MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Cell Host and Microbe' source. Mon, 06 Feb 2012 21:32:07 +0100 http://www.medworm.com/index.php?rid=5657618&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22284954%26dopt%3DAbstract Authors: Lim ES, Fregoso OI, McCoy CO, Matsen FA, Malik HS, Emerman M Abstract The human SAMHD1 protein potently restricts lentiviral infection in dendritic cells and monocyte/macrophages but is antagonized by the primate lentiviral protein Vpx, which targets SAMHD1 for degradation. However, only two of eight primate lentivirus lineages encode Vpx, whereas its paralog, Vpr, is conserved across all extant primate lentiviruses. We find that not only multiple Vpx but also some Vpr proteins are able to degrade SAMHD1, and such antagonism led to dramatic positive selection of SAMHD1 in the primate subfamily Cercopithecinae. Residues that have evolved under positive selection precisely determine sensitivity to Vpx/Vpr degradation and alter binding specificity. By overlaying these functio... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5657618 Tue, 24 Jan 2012 05:00:00 +0100 5657618 http://www.medworm.com/index.php?rid=5637816&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264506%26dopt%3DAbstract Authors: Kim K Abstract Plasmodium falciparum PfEMP1 is a malaria virulence protein whose expression is epigenetically regulated. The parasite's ability to express exclusively only one of the sixty var genes that encode PfEMP1 is essential for disease pathogenesis. Two recent papers identify key molecular players in determining whether a var gene is active or silenced (Volz et al., 2012; Zhang et al., 2011). PMID: 22264506 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5637816 Thu, 19 Jan 2012 05:00:00 +0100 5637816 http://www.medworm.com/index.php?rid=5637815&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264507%26dopt%3DAbstract Brucella "hitches a ride" with autophagy. Cell Host Microbe. 2012 Jan 19;11(1):2-4 Authors: Brumell JH Abstract Autophagy involves lysosomal-mediated degradation of cellular components and contributes to host immunity. Some pathogens avoid autophagy-mediated killing, while others exploit it to acquire host cell nutrients. Starr et al. reveal that the intracellular bacterial pathogen Brucella abortus can "hitch a ride" with autophagy, subverting autophagy machinery to spread from cell to cell (Starr et al., 2012). PMID: 22264507 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5637815 Thu, 19 Jan 2012 05:00:00 +0100 5637815 http://www.medworm.com/index.php?rid=5637814&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264508%26dopt%3DAbstract Authors: Justice SS, Hunstad DA Abstract During acute cystitis, uropathogenic Escherichia coli (UPEC) induce bladder epithelial cell exfoliation, which eliminates infected cells and promotes UPEC dissemination. Dhakal and Mulvey (2012) uncover the mechanism that induces this exfoliation and reintroduce the pore-forming toxin, hemolysin, as an effector that surprisingly targets multiple host pathways to facilitate infection. PMID: 22264508 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5637814 Thu, 19 Jan 2012 05:00:00 +0100 5637814 http://www.medworm.com/index.php?rid=5637813&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264509%26dopt%3DAbstract We report the identification of a parasite protein, designated PfSET10, which localizes exclusively to the perinuclear active var gene expression site. PfSET10 is a histone 3 lysine 4 methyltransferase required to maintain the active var gene in a poised state during division for reactivation in daughter parasites, and as such is required for P. falciparum antigenic variation. PfSET10 likely maintains the transcriptionally permissive chromatin environment of the active var promoter and thus retains memory for heritable transmission of epigenetic information during parasite division. PMID: 22264509 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5637813 Thu, 19 Jan 2012 05:00:00 +0100 5637813 http://www.medworm.com/index.php?rid=5637812&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264510%26dopt%3DAbstract Authors: Müller AJ, Kaiser P, Dittmar KE, Weber TC, Haueter S, Endt K, Songhet P, Zellweger C, Kremer M, Fehling HJ, Hardt WD Abstract Salmonella Typhimurium causes diarrhea by infecting the epithelium and lamina propria of the intestinal mucosa and by secreting various effector proteins through type III secretion systems (TTSSs). However, the mechanisms by which Salmonella transverses the epithelium and is subsequently released into the lamina propria are poorly understood. Using a murine Salmonella-diarrhea model and in vivo microscopy, we show that epithelial traversal requires TTSS-1-mediated invasion and TTSS-2-dependent trafficking to the basolateral side. After being released into the lamina propria, the bacterium is transiently extracellular before being taken up by phag... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5637812 Thu, 19 Jan 2012 05:00:00 +0100 5637812 http://www.medworm.com/index.php?rid=5637811&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264511%26dopt%3DAbstract Authors: Starr T, Child R, Wehrly TD, Hansen B, Hwang S, López-Otin C, Virgin HW, Celli J Abstract Autophagy is a cellular degradation process that can capture and eliminate intracellular microbes by delivering them to lysosomes for destruction. However, pathogens have evolved mechanisms to subvert this process. The intracellular bacterium Brucella abortus ensures its survival by forming the Brucella-containing vacuole (BCV), which traffics from the endocytic compartment to the endoplasmic reticulum (ER), where the bacterium proliferates. We show that Brucella replication in the ER is followed by BCV conversion into a compartment with autophagic features (aBCV). While Brucella trafficking to the ER was unaffected in autophagy-deficient cells, aBCV formation required the autophag... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5637811 Thu, 19 Jan 2012 05:00:00 +0100 5637811 http://www.medworm.com/index.php?rid=5637810&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264512%26dopt%3DAbstract Authors: Arasaki K, Toomre DK, Roy CR Abstract The intracellular bacterial pathogen Legionella pneumophila subverts host membrane transport pathways to promote fusion of vesicles exiting the endoplasmic reticulum (ER) with the pathogen-containing vacuole. During infection there is noncanonical pairing of the SNARE protein Sec22b on ER-derived vesicles with plasma membrane (PM)-localized syntaxin proteins on the vacuole. We show that the L. pneumophila Rab1-targeting effector DrrA is sufficient to stimulate this noncanonical SNARE association and promote membrane fusion. DrrA activation of the Rab1 GTPase on PM-derived organelles stimulated the tethering of ER-derived vesicles with the PM-derived organelle, resulting in vesicle fusion through the pairing of Sec22b with the PM synta... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5637810 Thu, 19 Jan 2012 05:00:00 +0100 5637810 http://www.medworm.com/index.php?rid=5637809&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264513%26dopt%3DAbstract Authors: Dhakal BK, Mulvey MA Abstract Uropathogenic Escherichia coli (UPEC), which are the leading cause of both acute and chronic urinary tract infections, often secrete a labile pore-forming toxin known as α-hemolysin (HlyA). We show that stable insertion of HlyA into epithelial cell and macrophage membranes triggers degradation of the cytoskeletal scaffolding protein paxillin and other host regulatory proteins, as well as components of the proinflammatory NFκB signaling cascade. Proteolysis of these factors requires host serine proteases, and paxillin degradation specifically involves the serine protease mesotrypsin. The induced activation of mesotrypsin by HlyA is preceded by redistribution of mesotrypsin precursors from the cytosol into foci along microtubules and within nu... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5637809 Thu, 19 Jan 2012 05:00:00 +0100 5637809 http://www.medworm.com/index.php?rid=5637808&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264514%26dopt%3DAbstract Authors: Lizak M, Yarovinsky TO Abstract The opportunistic gram-positive pathogen Staphylococcus aureus is a leading cause of pneumonia and sepsis. Staphylococcal α-toxin, a prototypical pore-forming toxin, is a major virulence factor of S. aureus clinical isolates, and lung epithelial cells are highly sensitive to α-toxin's cytolytic activity. Type I interferon (IFN) signaling activated in response to S. aureus increases pulmonary cell resistance to α-toxin, but the underlying mechanisms are uncharacterized. We show that IFNα protects human lung epithelial cells from α-toxin-induced intracellular ATP depletion and cell death by reducing extracellular ATP leakage. This effect depends on protein palmitoylation and induction of phospholipid scramblase 1 (PLSCR1). IFNα-induce... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5637808 Thu, 19 Jan 2012 05:00:00 +0100 5637808 http://www.medworm.com/index.php?rid=5637807&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264515%26dopt%3DAbstract Authors: Blomgran R, Desvignes L, Briken V, Ernst JD Abstract Mycobacterium tuberculosis promotes its replication by inhibiting the apoptosis of infected macrophages. A proapoptotic M. tuberculosis mutant lacking nuoG, a subunit of the type I NADH dehydrogenase complex, exhibits attenuated growth in vivo, indicating that this virulence mechanism is essential. We show that M. tuberculosis also suppresses neutrophil apoptosis. Compared to wild-type, the nuoG mutant spread to a larger number of lung phagocytic cells. Consistent with the shorter lifespan of infected neutrophils, infection with the nuoG mutant resulted in fewer bacteria per infected neutrophil, accelerated bacterial acquisition by dendritic cells, earlier trafficking of these dendritic cells to lymph nodes, and faste... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5637807 Thu, 19 Jan 2012 05:00:00 +0100 5637807 http://www.medworm.com/index.php?rid=5637806&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264516%26dopt%3DAbstract We examined the evolutionary dynamics of the A3G-Vif interaction within four African green monkey (AGM) subspecies, which are each naturally infected with a distinct simian immunodeficiency virus (SIV). We identified single amino acid changes within A3G in two AGM subspecies that render it resistant to Vif proteins, except for Vif from the viruses that naturally infect these subspecies. Moreover, experimental infection of AGMs shows that Vif can rapidly adapt to these arising Vif-resistant A3G genotypes. These data suggest that despite being generally nonpathogenic in its natural host, SIV infection selects for Vif-resistant forms of A3G in AGM populations, driving Vif counterevolution and functional divergence. PMID: 22264516 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5637806 Thu, 19 Jan 2012 05:00:00 +0100 5637806 http://www.medworm.com/index.php?rid=5530997&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169508%26dopt%3DAbstract We report the crystal structure of the AvrPtoB-BAK1 complex, which revealed structural similarity between these two AvrPtoB domains, suggesting that they arose by intragenic duplication. The BAK1 kinase domain is structurally similar to Pto, and a conserved region within both BAK1 and Pto interacts with AvrPtoB. BAK1 kinase activity is inhibited by AvrPtoB, and mutations at the interaction interface disrupt AvrPtoB virulence activity. These results shed light on a structural mechanism underlying host-pathogen coevolution. PMID: 22169508 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5530997 Thu, 15 Dec 2011 05:00:00 +0100 5530997 http://www.medworm.com/index.php?rid=5530996&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177555%26dopt%3DAbstract Authors: Thali M Abstract Rather than being separated by discrete boundaries, the different phases of viral replication cycles partially overlap one another. In this issue, Dale et al. (2011) describe a remarkable example of this phenomenon: HIV-1 matures, and thus becomes infectious, but only after it has already started entering target cells. PMID: 22177555 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5530996 Thu, 15 Dec 2011 05:00:00 +0100 5530996 http://www.medworm.com/index.php?rid=5530995&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177556%26dopt%3DAbstract Authors: Mesri EA, Cesarman E Abstract Culture of KSHV-infected lymphatic endothelial cells in 3D increases viral gene expression, leading to Notch-induced MT1-MMP-dependent endothelial-to-mesenchymal transition. This reproduces patterns of KSHV gene expression and presence of mesenchymal KSHV-infected cells found in KS lesions, narrowing the gap between in vitro systems of infection and KSHV tumorigenesis. PMID: 22177556 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5530995 Thu, 15 Dec 2011 05:00:00 +0100 5530995 http://www.medworm.com/index.php?rid=5530994&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177557%26dopt%3DAbstract Authors: Collins CR, Blackman MJ Abstract Host cell invasion by the malaria parasite is a crucial step in its life cycle. In this issue of Cell Host & Microbe, Giovannini et al. (2011) raise questions about the validity of a widely accepted model of the tight junction, a ring-like structure through which the invading parasite passes. PMID: 22177557 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5530994 Thu, 15 Dec 2011 05:00:00 +0100 5530994 http://www.medworm.com/index.php?rid=5530993&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177558%26dopt%3DAbstract Authors: Seo JY, Yaneva R, Cresswell P Abstract Viperin is an interferon-inducible protein that inhibits the replication of a variety of viruses by apparently diverse mechanisms. In some circumstances, it also plays a role in intracellular signaling pathways. Its expression in mitochondria, revealed by infection with human cytomegalovirus, also affects cellular metabolic pathways. We review here the current status of our understanding of this unusual molecule. PMID: 22177558 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5530993 Thu, 15 Dec 2011 05:00:00 +0100 5530993 http://www.medworm.com/index.php?rid=5530992&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177559%26dopt%3DAbstract Authors: Roan NR, Müller JA, Liu H, Chu S, Arnold F, Stürzel CM, Walther P, Dong M, Witkowska HE, Kirchhoff F, Münch J, Greene WC Abstract Semen serves as a vehicle for HIV and promotes sexual transmission of the virus, which accounts for the majority of new HIV cases. The major component of semen is the coagulum, a viscous structure composed predominantly of spermatozoa and semenogelin proteins. Due to the activity of the semen protease PSA, the coagulum is liquefied and semenogelins are cleaved into smaller fragments. Here, we report that a subset of these semenogelin fragments form amyloid fibrils that greatly enhance HIV infection. Like SEVI, another amyloid fibril previously identified in semen, the semenogelin fibrils exhibit a cationic surface and enhance HIV virion attac... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5530992 Thu, 15 Dec 2011 05:00:00 +0100 5530992 http://www.medworm.com/index.php?rid=5530991&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177560%26dopt%3DAbstract Authors: Dale BM, McNerney GP, Thompson DL, Hubner W, de Los Reyes K, Chuang FY, Huser T, Chen BK Abstract HIV-1 can infect T cells by cell-free virus or by direct virion transfer between cells through cell contact-induced structures called virological synapses (VS). During VS-mediated infection, virions accumulate within target cell endosomes. We show that after crossing the VS, the transferred virus undergoes both maturation and viral membrane fusion. Following VS transfer, viral membrane fusion occurs with delayed kinetics and transferred virions display reduced sensitivity to patient antisera compared to mature, cell-free virus. Furthermore, particle fusion requires that the transferred virions undergo proteolytic maturation within acceptor cell endosomes, which occurs over se... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5530991 Thu, 15 Dec 2011 05:00:00 +0100 5530991 http://www.medworm.com/index.php?rid=5530990&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177561%26dopt%3DAbstract Authors: Nonnenmacher M, Weber T Abstract Adeno-associated viruses (AAVs) are nonpathogenic, nonenveloped, single-stranded DNA viruses in development as gene therapy vectors. AAV internalization was postulated to proceed via a dynamin-dependent endocytic mechanism. Revisiting this, we find that infectious endocytosis of the prototypical AAV, AAV2, is independent of clathrin, caveolin, and dynamin. AAV2 infection is sensitive to EIPA, a fluid-phase uptake inhibitor, but is unaffected by Rac1 mutants or other macropinocytosis inhibitors. In contrast, AAV2 infection requires actin cytoskeleton remodeling and membrane cholesterol and is sensitive to inhibition of Cdc42, Arf1, and GRAF1, factors known to be involved in the formation of clathrin-independent carriers (CLIC). AAV2 virion... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5530990 Thu, 15 Dec 2011 05:00:00 +0100 5530990 http://www.medworm.com/index.php?rid=5530989&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177562%26dopt%3DAbstract Authors: Cheng F, Pekkonen P, Laurinavicius S, Sugiyama N, Henderson S, Günther T, Rantanen V, Kaivanto E, Aavikko M, Sarek G, Hautaniemi S, Biberfeld P, Aaltonen L, Grundhoff A, Boshoff C, Alitalo K, Lehti K, Ojala PM Abstract Kaposi sarcoma (KS), an angioproliferative disease associated with Kaposi sarcoma herpesvirus (KSHV) infection, harbors a diversity of cell types ranging from endothelial to mesenchymal cells of unclear origin. We developed a three-dimensional cell model for KSHV infection and used it to demonstrate that KSHV induces transcriptional reprogramming of lymphatic endothelial cells to mesenchymal cells via endothelial-to-mesenchymal transition (EndMT). KSHV-induced EndMT was initiated by the viral proteins vFLIP and vGPCR through Notch pathway activation, leadi... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5530989 Thu, 15 Dec 2011 05:00:00 +0100 5530989 http://www.medworm.com/index.php?rid=5530988&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177563%26dopt%3DAbstract Authors: Giovannini D, Späth S, Lacroix C, Perazzi A, Bargieri D, Lagal V, Lebugle C, Combe A, Thiberge S, Baldacci P, Tardieux I, Ménard R Abstract During invasion, apicomplexan parasites form an intimate circumferential contact with the host cell, the tight junction (TJ), through which they actively glide. The TJ, which links the parasite motor to the host cell cytoskeleton, is thought to be composed of interacting apical membrane antigen 1 (AMA1) and rhoptry neck (RON) proteins. Here we find that, in Plasmodium berghei, while both AMA1 and RON4 are important for merozoite invasion of erythrocytes, only RON4 is required for sporozoite invasion of hepatocytes, indicating that RON4 acts independently of AMA1 in the sporozoite. Further, in the Toxoplasma gondii tachyzoite, AMA1 is... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5530988 Thu, 15 Dec 2011 05:00:00 +0100 5530988 http://www.medworm.com/index.php?rid=5530987&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177564%26dopt%3DAbstract Authors: Li X, Utomo A, Cullere X, Choi MM, Milner DA, Venkatesh D, Yun SH, Mayadas TN Abstract Resistance to fungal infections is attributed to engagement of host pattern-recognition receptors, notably the β-glucan receptor Dectin-1 and the integrin Mac-1, which induce phagocytosis and antifungal immunity. However, the mechanisms by which these receptors coordinate fungal clearance are unknown. We show that upon ligand binding, Dectin-1 activates Mac-1 to also recognize fungal components, and this stepwise process is critical for neutrophil cytotoxic responses. Both Mac-1 activation and Dectin-1- and Mac-1-induced neutrophil effector functions require Vav1 and Vav3, exchange factors for RhoGTPases. Mac-1- or Vav1,3-deficient mice have increased susceptibility to systemic candidia... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5530987 Thu, 15 Dec 2011 05:00:00 +0100 5530987 http://www.medworm.com/index.php?rid=5530986&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177565%26dopt%3DAbstract Authors: Lam GY, Fattouh R, Muise AM, Grinstein S, Higgins DE, Brumell JH Abstract The intracellular bacterial pathogen Listeria monocytogenes produces phospholipases C (PI-PLC and PC-PLC) and the pore-forming cytolysin listeriolysin O (LLO) to escape the phagosome and replicate within the host cytosol. We found that PLCs can also activate the phagocyte NADPH oxidase during L. monocytogenes infection, a response that would adversely affect pathogen survival. However, secretion of LLO inhibits the NADPH oxidase by preventing its localization to phagosomes. LLO-deficient bacteria can be complemented by perfringolysin O, a related cytolysin, suggesting that other pathogens may also use pore-forming cytolysins to inhibit the NADPH oxidase. Our studies demonstrate that while the PLCs ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5530986 Thu, 15 Dec 2011 05:00:00 +0100 5530986 http://www.medworm.com/index.php?rid=5438651&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100157%26dopt%3DAbstract Authors: Prlic M, Hohl TM Abstract Fungal cell wall polysaccharides are potent inducers of immune responses. Cohen et al. (2011) demonstrate that innate recognition of fungal β-(1,3) glucan triggers effector functions of invariant natural killer T (iNKT) cells through indirect, cytokine-driven activation, a process that mediates optimal protection against the opportunistic mold Aspergillus fumigatus. PMID: 22100157 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5438651 Thu, 17 Nov 2011 05:00:00 +0100 5438651 http://www.medworm.com/index.php?rid=5438650&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100158%26dopt%3DAbstract Authors: Honda K Abstract Periodontitis is linked to polymicrobial interactions and the presence of Porphyromonas gingivalis. In this issue of Cell Host & Microbe, Hajishengallis et al. (2011) demonstrate that P. gingivalis colonization in the oral cavity changes the composition of the oral commensal microbiota and accelerates microbiota-mediated bone-destructive periodontitis, indicating that this single, low-abundance species is a keystone in periodontal disease. PMID: 22100158 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5438650 Thu, 17 Nov 2011 05:00:00 +0100 5438650 http://www.medworm.com/index.php?rid=5438649&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100159%26dopt%3DAbstract Authors: Ott M, Geyer M, Zhou Q Abstract Thirteen years ago, human cyclin T1 was identified as part of the positive transcription elongation factor b (P-TEFb) and the long-sought host cofactor for the HIV-1 transactivator Tat. Recent years have brought new insights into the intricate regulation of P-TEFb function and its relationship with Tat, revealing novel mechanisms for controlling HIV transcription and fueling new efforts to overcome the barrier of transcriptional latency in eradicating HIV. Moreover, the improved understanding of HIV and Tat forms a basis for studying transcription elongation control in general. Here, we review advances in HIV transcription research with a focus on the growing family of cellular P-TEFb complexes, structural insights into the interactions betw... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5438649 Thu, 17 Nov 2011 05:00:00 +0100 5438649 http://www.medworm.com/index.php?rid=5438648&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100160%26dopt%3DAbstract Authors: Cohen NR, Tatituri RV, Rivera A, Watts GF, Kim EY, Chiba A, Fuchs BB, Mylonakis E, Besra GS, Levitz SM, Brigl M, Brenner MB Abstract iNKT cells are innate T lymphocytes recognizing endogenous and foreign lipid antigens presented in the MHC-like molecule CD1d. The semi-invariant iNKT cell TCR can detect certain bacterial and parasitic lipids and drive iNKT cell responses. How iNKT cells respond to fungi, however, is unknown. We found that CD1d-deficient mice, which lack iNKT cells, poorly control infection with the fungal pathogen Aspergillus fumigatus. Furthermore, A. fumigatus rapidly activates iNKT cells in vivo and in vitro in the presence of APCs. Surprisingly, despite a requirement for CD1d recognition, the antifungal iNKT cell response does not require fungal lipi... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5438648 Thu, 17 Nov 2011 05:00:00 +0100 5438648 http://www.medworm.com/index.php?rid=5438647&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100161%26dopt%3DAbstract Authors: Zhang Q, Huang Y, Zhang Y, Fang X, Claes A, Duchateau M, Namane A, Lopez-Rubio JJ, Pan W, Scherf A Abstract Many microbial pathogens, including the malaria parasite Plasmodium falciparum, vary surface protein expression to evade host immune responses. P. falciparium antigenic variation is linked to var gene family-encoded clonally variant surface protein expression. Mututally exclusive var gene expression is partially controlled by spatial positioning; silent genes are retained at distinct perinuclear sites and relocated to transcriptionally active locations for monoallelic expression. We show that var introns can control this process and that var intron addition relocalizes episomes from a random to a perinuclear position. This var intron-regulated nuclear tethering and ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5438647 Thu, 17 Nov 2011 05:00:00 +0100 5438647 http://www.medworm.com/index.php?rid=5438646&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100162%26dopt%3DAbstract Authors: Maddugoda MP, Stefani C, Gonzalez-Rodriguez D, Saarikangas J, Torrino S, Janel S, Munro P, Doye A, Prodon F, Aurrand-Lions M, Goossens PL, Lafont F, Bassereau P, Lappalainen P, Brochard F, Lemichez E Abstract RhoA-inhibitory bacterial toxins, such as Staphylococcus aureus EDIN toxin, induce large transendothelial cell macroaperture (TEM) tunnels that rupture the host endothelium barrier and promote bacterial dissemination. Host cells repair these tunnels by extending actin-rich membrane waves from the TEM edges. We reveal that cyclic-AMP signaling produced by Bacillus anthracis edema toxin (ET) also induces TEM formation, which correlates with increased vascular permeability. We show that ET-induced TEM formation resembles liquid dewetting, a physical process of nucleation... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5438646 Thu, 17 Nov 2011 05:00:00 +0100 5438646 http://www.medworm.com/index.php?rid=5438645&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100163%26dopt%3DAbstract Authors: Napier RJ, Rafi W, Cheruvu M, Powell KR, Zaunbrecher MA, Bornmann W, Salgame P, Shinnick TM, Kalman D Abstract The lengthy course of treatment with currently used antimycobacterial drugs and the resulting emergence of drug-resistant strains have intensified the need for alternative therapies against Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis. We show that Mtb and Mycobacterium marinum use ABL and related tyrosine kinases for entry and intracellular survival in macrophages. In mice, the ABL family tyrosine kinase inhibitor, imatinib (Gleevec), when administered prophylactically or therapeutically, reduced both the number of granulomatous lesions and bacterial load in infected organs and was also effective against a rifampicin-resistant strain. Fur... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5438645 Thu, 17 Nov 2011 05:00:00 +0100 5438645 http://www.medworm.com/index.php?rid=5438644&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100164%26dopt%3DAbstract Authors: Dalia AB, Weiser JN Abstract The complement system, which functions by lysing pathogens directly or by promoting their uptake by phagocytes, is critical for controlling many microbial infections. Here, we show that in Streptococcus pneumoniae, increasing bacterial chain length sensitizes this pathogen to complement deposition and subsequent uptake by human neutrophils. Consistent with this, we show that minimizing chain length provides wild-type bacteria with a competitive advantage in vivo in a model of systemic infection. Investigating how the host overcomes this virulence strategy, we find that antibody promotes complement-dependent opsonophagocytic killing of Streptococcus pneumoniae and lysis of Haemophilus influenzae independent of Fc-mediated effector functions. Co... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5438644 Thu, 17 Nov 2011 05:00:00 +0100 5438644 http://www.medworm.com/index.php?rid=5438643&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100165%26dopt%3DAbstract Authors: Gottwein E, Corcoran DL, Mukherjee N, Skalsky RL, Hafner M, Nusbaum JD, Shamulailatpam P, Love CL, Dave SS, Tuschl T, Ohler U, Cullen BR Abstract Primary effusion lymphoma (PEL) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV) and frequently also harbors Epstein-Barr virus (EBV). The expression of KSHV- and EBV-encoded microRNAs (miRNAs) in PELs suggests a role for these miRNAs in latency and lymphomagenesis. Using PAR-CLIP, a technology which allows the direct and transcriptome-wide identification of miRNA targets, we delineate the target sites for all viral and cellular miRNAs expressed in PEL cell lines. The resulting data set revealed that KSHV miRNAs directly target more than 2000 cellular mRNAs, including many involved in pathways relevant to KSHV pathogen... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5438643 Thu, 17 Nov 2011 05:00:00 +0100 5438643 http://www.medworm.com/index.php?rid=5378852&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22036470%26dopt%3DAbstract Authors: Marcobal A, Barboza M, Sonnenburg ED, Pudlo N, Martens EC, Desai P, Lebrilla CB, Weimer BC, Mills DA, German JB, Sonnenburg JL Abstract Newborns are colonized with an intestinal microbiota shortly after birth, but the factors governing the retention and abundance of specific microbial lineages are unknown. Nursing infants consume human milk oligosaccharides (HMOs) that pass undigested to the distal gut, where they may be digested by microbes. We determined that the prominent neonate gut residents, Bacteroides thetaiotaomicron and Bacteroides fragilis, induce the same genes during HMO consumption that are used to harvest host mucus glycans, which are structurally similar to HMOs. Lacto-N-neotetraose, a specific HMO component, selects for HMO-adapted species such as Bifidoba... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5378852 Wed, 26 Oct 2011 04:00:00 +0100 5378852 http://www.medworm.com/index.php?rid=5378853&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22036469%26dopt%3DAbstract Authors: Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, McIntosh ML, Alsam A, Kirkwood KL, Lambris JD, Darveau RP, Curtis MA Abstract Porphyromonas gingivalis is a low-abundance oral anaerobic bacterium implicated in periodontitis, a polymicrobial inflammatory disease, and the associated systemic conditions. However, the mechanism by which P. gingivalis contributes to inflammation and disease has remained elusive. Here we show that P. gingivalis, at very low colonization levels, triggers changes to the amount and composition of the oral commensal microbiota leading to inflammatory periodontal bone loss. The commensal microbiota and complement were both required for P. gingivalis-induced bone loss, as germ-free mice or conventionally raised C3a and C5a recept... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5378853 Tue, 25 Oct 2011 04:00:00 +0100 5378853 http://www.medworm.com/index.php?rid=5360407&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018226%26dopt%3DAbstract Microbes "r" us. Cell Host Microbe. 2011 Oct 4;10(4):285-6 Authors: PMID: 22018226 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360407 Tue, 04 Oct 2011 04:00:00 +0100 5360407 http://www.medworm.com/index.php?rid=5360406&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018227%26dopt%3DAbstract Authors: Proctor LM Abstract The human microbiome comprises the genes and genomes of the microbiota that inhabit the body. We highlight Human Microbiome Project (HMP) resources, including 600 microbial reference genomes, 70 million 16S sequences, 700 metagenomes, and 60 million predicted genes from healthy adult microbiomes. Microbiome studies of specific diseases and future research directions are also discussed. PMID: 22018227 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360406 Tue, 04 Oct 2011 04:00:00 +0100 5360406 http://www.medworm.com/index.php?rid=5360405&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018228%26dopt%3DAbstract Authors: Knights D, Parfrey LW, Zaneveld J, Lozupone C, Knight R Abstract Host-associated microbial communities are unique to individuals, affect host health, and correlate with disease states. Although advanced technologies capture detailed snapshots of microbial communities, high within- and between-subject variation hampers discovery of microbial signatures in diagnostic or forensic settings. We suggest turning to machine learning and discuss key directions toward harnessing human-associated microbial signatures. PMID: 22018228 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360405 Tue, 04 Oct 2011 04:00:00 +0100 5360405 http://www.medworm.com/index.php?rid=5360404&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018229%26dopt%3DAbstract Authors: Mathis D, Benoist C Abstract The trillions of microbial symbionts normally hosted by mammals have important influences on the development and function of the immune system. We highlight recently discovered cellular and molecular mechanisms by which they impact autoimmune diseases-in particular, gut-distal disorders. Besides provoking a reconsideration of the definition of immunological "self" and "nonself," these new findings evoke exciting possibilities for the discovery of a whole new class of immunomodulatory molecules. PMID: 22018229 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360404 Tue, 04 Oct 2011 04:00:00 +0100 5360404 http://www.medworm.com/index.php?rid=5360403&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018230%26dopt%3DAbstract Authors: Curtis MA, Zenobia C, Darveau RP Abstract The oral microbial community represents the best-characterized consortium associated with the human host. There are strong correlations between the qualitative composition of the oral microbiota and clinically healthy or diseased states. However, additional studies are needed to elucidate the mechanisms that define these microbial/host relationships. PMID: 22018230 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360403 Tue, 04 Oct 2011 04:00:00 +0100 5360403 http://www.medworm.com/index.php?rid=5360402&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018231%26dopt%3DAbstract Authors: Cirimotich CM, Ramirez JL, Dimopoulos G Abstract The resident microbiota of insect vectors can impede transmission of human pathogens. Recent studies have highlighted the capacity of endogenous bacteria to decrease viral and parasitic infections in mosquito and tsetse fly vectors by activating their immune responses or directly inhibiting pathogen development. These microbes may prove effective agents for manipulating the vector competence of malaria and other important human pathogens. PMID: 22018231 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360402 Tue, 04 Oct 2011 04:00:00 +0100 5360402 http://www.medworm.com/index.php?rid=5360401&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018232%26dopt%3DAbstract Authors: Littman DR, Pamer EG Abstract The commensal microbiota that inhabit different parts of the gastrointestinal (GI) tract have been shaped by coevolution with the host species. The symbiotic relationship of the hundreds of microbial species with the host requires a tuned response that prevents host damage, e.g., inflammation, while tolerating the presence of the potentially beneficial microbes. Recent studies have begun to shed light on immunological processes that participate in maintenance of homeostasis with the microbiota and on how disturbance of host immunity or the microbial ecosystem can result in disease-provoking dysbiosis. Our growing appreciation of this delicate host-microbe relationship promises to influence our understanding of inflammatory diseases and infecti... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360401 Tue, 04 Oct 2011 04:00:00 +0100 5360401 http://www.medworm.com/index.php?rid=5360400&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018233%26dopt%3DAbstract Authors: Plottel CS, Blaser MJ Abstract Current knowledge is insufficient to explain why only a proportion of individuals exposed to environmental carcinogens or carrying a genetic predisposition to cancer develop disease. Clearly, other factors must be important, and one such element that has recently received attention is the human microbiome, the residential microbes including Bacteria, Archaea, Eukaryotes, and viruses that colonize humans. Here, we review principles and paradigms of microbiome-related malignancy, as illustrated by three specific microbial-host interactions. We review the effects of the microbiota on local and adjacent neoplasia, present the estrobolome model of distant effects, and discuss the complex interactions with a latent virus leading to malignancy. Thes... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360400 Tue, 04 Oct 2011 04:00:00 +0100 5360400 http://www.medworm.com/index.php?rid=5360399&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018234%26dopt%3DAbstract Authors: Fischbach MA, Sonnenburg JL Abstract In bacterial communities, "tight economic times" are the norm. Of the many challenges bacteria face in making a living, perhaps none are more important than generating energy, maintaining redox balance, and acquiring carbon and nitrogen to synthesize primary metabolites. The ability of bacteria to meet these challenges depends heavily on the rest of their community. Indeed, the most fundamental way in which bacteria communicate is by importing the substrates for metabolism and exporting metabolic end products. As an illustration of this principle, we will travel down a carbohydrate catabolic pathway common to many species of Bacteroides, highlighting the interspecies interactions established (often inevitably) at its key steps. We also ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360399 Tue, 04 Oct 2011 04:00:00 +0100 5360399 http://www.medworm.com/index.php?rid=5360398&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018235%26dopt%3DAbstract Authors: Desbrosses GJ, Stougaard J Abstract Legume plants have an exceptional capacity for association with microorganisms, ranging from largely nonspecific to very specific interactions. Legume-rhizobial symbiosis results in major developmental and metabolic changes for both the microorganism and host, while providing the plant with fixed nitrogen. A complex signal exchange leads to the selective rhizobial colonization of plant cells within nodules, new organs that develop on the roots of host plants. Although the nodulation mechanism is highly specific, it involves the same subset of plant phytohormones, namely auxin, cytokinin, and ethylene, which are required for root development. In addition, nodulation triggered by the rhizobia affects the development of the host root system... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360398 Tue, 04 Oct 2011 04:00:00 +0100 5360398 http://www.medworm.com/index.php?rid=5360397&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018236%26dopt%3DAbstract Authors: Douglas AE Abstract As in mammals, insect health is strongly influenced by the composition and activities of resident microorganisms. However, the microbiota of insects is generally less diverse than that of mammals, allowing microbial function in insects to be coupled to individual, identified microbial species. This trait of insect symbioses facilitates our understanding of the mechanisms that promote insect-microbial coexistence and the processes by which the microbiota affect insect well-being. As a result, insects are potentially ideal models to study various aspects of interactions between the host and its resident microorganisms that would be impractical or unfeasible in mammals and to generate hypotheses for subsequent testing in mammalian models. PMID: 2201823... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360397 Tue, 04 Oct 2011 04:00:00 +0100 5360397 http://www.medworm.com/index.php?rid=5360391&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018237%26dopt%3DAbstract Authors: Holmes EC Abstract Endogenous retroviruses are a common component of the eukaryotic genome, and their evolution and potential function have attracted considerable interest. More surprising was the recent discovery that eukaryotic genomes contain sequences from RNA viruses that have no DNA stage in their life cycle. Similarly, several single-stranded DNA viruses have left integrated copies in their host genomes. This review explores some major evolutionary aspects arising from the discovery of these endogenous viral elements (EVEs). In particular, the reasons for the bias toward EVEs derived from negative-sense RNA viruses are considered, as well as what they tell us about the long-term "arms races" between hosts and viruses, characterized by episodes of selection and count... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360391 Tue, 04 Oct 2011 04:00:00 +0100 5360391 http://www.medworm.com/index.php?rid=5360380&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018238%26dopt%3DAbstract Authors: Andrei G, Lisco A, Vanpouille C, Introini A, Balestra E, van den Oord J, Cihlar T, Perno CF, Snoeck R, Margolis L, Balzarini J Abstract The HIV reverse-transcriptase inhibitor, tenofovir, was recently formulated into a vaginal gel for use as a microbicide. In human trials, a 1% tenofovir gel inhibited HIV sexual transmission by 39% and, surprisingly, herpes simplex virus-2 (HSV-2) transmission by 51%. We demonstrate that the concentration achieved intravaginally with a 1% tenofovir topical gel has direct antiherpetic activity. Tenofovir inhibits the replication of HSV clinical isolates in human embryonic fibroblasts, keratinocytes, and organotypic epithelial 3D rafts, decreases HSV replication in human lymphoid and cervicovaginal tissues ex vivo, and delays HSV-induced le... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360380 Tue, 04 Oct 2011 04:00:00 +0100 5360380 http://www.medworm.com/index.php?rid=5360362&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018239%26dopt%3DAbstract Authors: Li R, Zhu J, Xie Z, Liao G, Liu J, Chen MR, Hu S, Woodard C, Lin J, Taverna SD, Desai P, Ambinder RF, Hayward GS, Qian J, Zhu H, Hayward SD Abstract Herpesviruses, which are major human pathogens, establish life-long persistent infections. Although the α, β, and γ herpesviruses infect different tissues and cause distinct diseases, they each encode a conserved serine/threonine kinase that is critical for virus replication and spread. The extent of substrate conservation and the key common cell-signaling pathways targeted by these kinases are unknown. Using a human protein microarray high-throughput approach, we identify shared substrates of the conserved kinases from herpes simplex virus, human cytomegalovirus, Epstein-Barr virus (EBV), and Kaposi's sarcoma-associated h... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360362 Tue, 04 Oct 2011 04:00:00 +0100 5360362 http://www.medworm.com/index.php?rid=5360355&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018240%26dopt%3DAbstract Authors: Hiyoshi H, Kodama T, Saito K, Gotoh K, Matsuda S, Akeda Y, Honda T, Iida T Abstract Vibrio parahaemolyticus, a Gram-negative halophilic bacterium that causes acute gastroenteritis in humans, is characterized by two type III secretion systems (T3SS), namely T3SS1 and T3SS2. T3SS2 is indispensable for enterotoxicity but the effector(s) involved are unknown. Here, we identify VopV as a critical effector that is required to mediate V. parahaemolyticus T3SS2-dependent enterotoxicity. VopV was found to possess multiple F-actin-binding domains and the enterotoxicity caused by VopV correlated with its F-actin-binding activity. Furthermore, a T3SS2-related secretion system and a vopV homologous gene were also involved in the enterotoxicity of a non-O1/non-O139 V. cholerae strain.... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360355 Tue, 04 Oct 2011 04:00:00 +0100 5360355 http://www.medworm.com/index.php?rid=5360354&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018241%26dopt%3DAbstract Authors: Treeck M, Sanders JL, Elias JE, Boothroyd JC Abstract Plasmodium falciparum and Toxoplasma gondii are obligate intracellular apicomplexan parasites that rapidly invade and extensively modify host cells. Protein phosphorylation is one mechanism by which these parasites can control such processes. Here we present a phosphoproteome analysis of peptides enriched from schizont stage P. falciparum and T. gondii tachyzoites that are either "intracellular" or purified away from host material. Using liquid chromatography-tandem mass spectrometry, we identified over 5,000 and 10,000 previously unknown phosphorylation sites in P. falciparum and T. gondii, respectively, revealing that protein phosphorylation is an extensively used regulation mechanism both within and beyond parasi... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5360354 Tue, 04 Oct 2011 04:00:00 +0100 5360354 http://www.medworm.com/index.php?rid=5244906&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925103%26dopt%3DAbstract Authors: Gack MU Abstract Tripartite motif (TRIM) proteins are novel players in antiviral innate immunity. In this issue of Cell Host & Microbe,Taylor et al. (2011) discover the mechanism of action of TRIM79α and show that this interferon-induced protein restricts tick-borne flaviviruses by targeting the viral polymerase for degradation. PMID: 21925103 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5244906 Thu, 15 Sep 2011 04:00:00 +0100 5244906 http://www.medworm.com/index.php?rid=5244905&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925104%26dopt%3DAbstract Authors: Eisenberg RJ, Cairns TM, Cohen GH Abstract The HCMV-neutralizing monoclonal antibody MSL-109 failed to prevent HCMV-induced disease in the clinic. In this issue of Cell Host & Microbe, Manley et al. (2011) found that MSL-109 rapidly induces antibody resistance by a nongenetic mechanism. Their results shed light on how antibodies can interact with their targets both outside and inside infected cells and virions. PMID: 21925104 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5244905 Thu, 15 Sep 2011 04:00:00 +0100 5244905 http://www.medworm.com/index.php?rid=5244904&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925105%26dopt%3DAbstract Authors: Lencer WI, Tweten RK Abstract The botulinum toxins (BoNTs) enter the cytosol of host cells by translocation across the limiting membrane of acidic endosomes. In this issue, Sun et al. (2011) show that BoNT binding to one of its cell surface receptors renders it susceptible to pH-dependent conformational changes required for translocation and cellular toxicity. PMID: 21925105 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5244904 Thu, 15 Sep 2011 04:00:00 +0100 5244904 http://www.medworm.com/index.php?rid=5244903&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925106%26dopt%3DAbstract Authors: Russell DG Abstract Evolving under constant threat from invading microbes, macrophages have acquired multiple means of killing bacteria. In this issue of Cell Host & Microbe, Botella and colleagues (Botella et al., 2011) describe a novel antimicrobial mechanism based on elevated levels of intraphagosomal Zn(2+) and the corresponding induction of bacterial genes to ameliorate this host-derived stress. PMID: 21925106 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5244903 Thu, 15 Sep 2011 04:00:00 +0100 5244903 http://www.medworm.com/index.php?rid=5244902&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925107%26dopt%3DAbstract Authors: Taylor RT, Lubick KJ, Robertson SJ, Broughton JP, Bloom ME, Bresnahan WA, Best SM Abstract In response to virus infection, type I interferons (IFNs) induce several genes, most of whose functions are largely unknown. Here, we show that the tripartite motif (TRIM) protein, TRIM79α, is an IFN-stimulated gene (ISG) product that specifically targets tick-borne encephalitis virus (TBEV), a Flavivirus that causes encephalitides in humans. TRIM79α restricts TBEV replication by mediating lysosome-dependent degradation of the flavivirus NS5 protein, an RNA-dependent RNA polymerase essential for virus replication. NS5 degradation was specific to tick-borne flaviviruses, as TRIM79α did not recognize NS5 from West Nile virus (WNV) or inhibit WNV replication. In the absence of TRIM79... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5244902 Thu, 15 Sep 2011 04:00:00 +0100 5244902 http://www.medworm.com/index.php?rid=5244901&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925108%26dopt%3DAbstract Authors: Manley K, Anderson J, Yang F, Szustakowski J, Oakeley EJ, Compton T, Feire AL Abstract Human cytomegalovirus (CMV) is a common but difficult to treat infection of immunocompromised patients. MSL-109 is a human monoclonal IgG isolated from a CMV seropositive individual that recognizes the viral glycoprotein H (gH) surface antigen complexes that mediate entry. Although MSL-109 blocks CMV infection in vitro, it lacked sufficient efficacy in human trials, and CMV isolated from treated patients suggested the evolution of MSL-109 resistance. To understand how CMV escapes MSL-109, we characterized a MSL-109-resistant CMV strain. Our results elucidate a nongenetic escape mechanism in which the antibody is selectively taken up by infected cells and incorporated into assembling vir... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5244901 Thu, 15 Sep 2011 04:00:00 +0100 5244901 http://www.medworm.com/index.php?rid=5244900&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925109%26dopt%3DAbstract We report a microtubule motor kinesin-1-mediated and NPC-supported mechanism of adenovirus uncoating. The capsid binds to the NPC filament protein Nup214 and kinesin-1 light-chain Klc1/2. The nucleoporin Nup358, which is bound to Nup214/Nup88, interacts with the kinesin-1 heavy-chain Kif5c to indirectly link the capsid to the kinesin motor. Kinesin-1 disrupts capsids docked at Nup214, which compromises the NPC and dislocates nucleoporins and capsid fragments into the cytoplasm. NPC disruption increases nuclear envelope permeability as indicated by the nuclear influx of large cytoplasmic dextran polymers. Thus, kinesin-1 uncoats viral DNA and compromises NPC integrity, allowing viral genomes nuclear access to promote infection. PMID: 21925109 [PubMed - in process] (Source: Cell Host a... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5244900 Thu, 15 Sep 2011 04:00:00 +0100 5244900 http://www.medworm.com/index.php?rid=5244899&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925110%26dopt%3DAbstract Authors: Whitmarsh RJ, Gray CM, Gregg B, Christian DA, May MJ, Murray PJ, Hunter CA Abstract The innate and adaptive immune responses that confer resistance to the intracellular pathogen Toxoplasma gondii critically depend on IL-12 production, which drives interferon-γ (IFN-γ) expression. Certain cytokines can activate STAT3 and limit IL-12 production to prevent infection-associated immune pathology, but T. gondii also directly activates STAT3 to evade host immunity. We show that suppressor of cytokine signaling molecule 3 (SOCS3), a target of STAT3 that limits signaling by the pleiotropic cytokine IL-6, is upregulated in response to infection but is dispensable for the immune-inhibitory effects of T. gondii. Unexpectedly, mice with targeted deletion of SOCS3 in macrophages an... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5244899 Thu, 15 Sep 2011 04:00:00 +0100 5244899 http://www.medworm.com/index.php?rid=5244898&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925111%26dopt%3DAbstract Authors: Sun S, Suresh S, Liu H, Tepp WH, Johnson EA, Edwardson JM, Chapman ER Abstract Botulinum neurotoxins (BoNTs, serotypes A-G), elaborated by Clostridium botulinum, can induce lethal paralysis and are classified as Category A bioterrorism agents. However, how BoNTs translocate from endosomes into the cytosol of neurons to gain access to their intracellular targets remains enigmatic. We discovered that binding to the ganglioside GT1b, a toxin coreceptor, enables BoNT/B to sense low pH, undergo a significant change in secondary structure, and transform into a hydrophobic oligomeric membrane protein. Imaging of the toxin on lipid bilayers using atomic force microscopy revealed donut-shaped channel-like structures that resemble other protein translocation assemblies. Toosendanin,... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5244898 Thu, 15 Sep 2011 04:00:00 +0100 5244898 http://www.medworm.com/index.php?rid=5244897&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925112%26dopt%3DAbstract Authors: Botella H, Peyron P, Levillain F, Poincloux R, Poquet Y, Brandli I, Wang C, Tailleux L, Tilleul S, Charrière GM, Waddell SJ, Foti M, Lugo-Villarino G, Gao Q, Maridonneau-Parini I, Butcher PD, Castagnoli PR, Gicquel B, de Chastellier C, Neyrolles O Abstract Mycobacterium tuberculosis thrives within macrophages by residing in phagosomes and preventing them from maturing and fusing with lysosomes. A parallel transcriptional survey of intracellular mycobacteria and their host macrophages revealed signatures of heavy metal poisoning. In particular, mycobacterial genes encoding heavy metal efflux P-type ATPases CtpC, CtpG, and CtpV, and host cell metallothioneins and zinc exporter ZnT1, were induced during infection. Consistent with this pattern of gene modulation, we observed... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5244897 Thu, 15 Sep 2011 04:00:00 +0100 5244897 http://www.medworm.com/index.php?rid=5244896&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925113%26dopt%3DAbstract We present the genome sequence of SFB isolated from monocolonized mice, which classifies SFB phylogenetically as a unique member of Clostridiales with a highly reduced genome. Annotation analysis demonstrates that SFB depend on their environment for amino acids and essential nutrients and may utilize host and dietary glycans for carbon, nitrogen, and energy. Comparative analyses reveal that SFB are functionally related to members of the genus Clostridium and several pathogenic or commensal "minimal" genera, including Finegoldia, Mycoplasma, Borrelia, and Phytoplasma. However, SFB are functionally distinct from all 1200 examined genomes, indicating a gene complement representing biology relatively unique to their role as a gut commensal closely tied to host metabolism and immunity. PMID... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5244896 Thu, 15 Sep 2011 04:00:00 +0100 5244896 http://www.medworm.com/index.php?rid=5244895&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925114%26dopt%3DAbstract We present the complete genome sequences of both rat and mouse SFB isolated from SFB-monocolonized hosts. The rat and mouse SFB genomes each harbor a single circular chromosome of 1.52 and 1.59 Mb encoding 1346 and 1420 protein-coding genes, respectively. The overall nucleotide identity between the two genomes is 86%, and the substitution rate was estimated to be similar to that of the free-living E. coli. SFB genomes encode typical genes for anaerobic fermentation and spore and flagella formation, but lack most of the amino acid biosynthesis enzymes, reminiscent of pathogenic Clostridia, exhibiting large dependency on the host. However, SFB lack most of the clostridial virulence-related genes. Comparative analysis with clostridial genomes suggested possible mechanisms for host responses ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5244895 Thu, 15 Sep 2011 04:00:00 +0100 5244895 http://www.medworm.com/index.php?rid=5140801&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843863%26dopt%3DAbstract Authors: Itzen A, Goody RS Abstract Adenylylation of Rab proteins appears to be an intriguing mechanism that Legionella pneumophila uses to modulate their activity during infection. Now the reverse reaction (deadenylylation) (Neunuebel et al., 2011; Tan and Luo, 2011) and a new posttranslational modification (phosphocholination) of Rab1 (Mukherjee et al., 2011) have been reported. PMID: 21843863 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5140801 Wed, 17 Aug 2011 23:00:00 +0100 5140801 http://www.medworm.com/index.php?rid=5140800&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843864%26dopt%3DAbstract Authors: Stiles KM, Kielian M Abstract The identity of the receptors that mediate alphavirus entry into host cells has been elusive. In this issue of Cell Host & Microbe, Rose et al. (2011) use a Drosophila RNAi screen to identify NRAMP, an iron transporter with 12 transmembrane domains, as a receptor for Sindbis virus in both insect and mammalian cells. PMID: 21843864 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5140800 Wed, 17 Aug 2011 23:00:00 +0100 5140800 http://www.medworm.com/index.php?rid=5140799&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843865%26dopt%3DAbstract Authors: Blankenship JR, Mitchell AP Abstract The pathogen Candida albicans can occupy both the bloodstream and gastrointesintal (GI) tract, niches that differ in iron availability. Chen et al. report that a distinct transcription factor, Sef1, alters the conserved fungal iron regulatory paradigm. Sef1 is pivotal for bloodstream infection, but contributes to GI tract colonization as well. PMID: 21843865 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5140799 Wed, 17 Aug 2011 23:00:00 +0100 5140799 http://www.medworm.com/index.php?rid=5140798&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843866%26dopt%3DAbstract Authors: Marconi RT, McDowell JV Abstract The ability of the Lyme disease spirochetes to establish an infection in mammals is dependent in part on proteins of tick origin. Schuijt et al. (2011) investigate the role of the tick-derived protein, TSLPI, in spirochete transmission and in the evasion of killing by the lectin complement pathway. PMID: 21843866 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5140798 Wed, 17 Aug 2011 23:00:00 +0100 5140798 http://www.medworm.com/index.php?rid=5140797&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843867%26dopt%3DAbstract Authors: Rose PP, Hanna SL, Spiridigliozzi A, Wannissorn N, Beiting DP, Ross SR, Hardy RW, Bambina SA, Heise MT, Cherry S Abstract Alphaviruses, including several emerging human pathogens, are a large family of mosquito-borne viruses with Sindbis virus being a prototypical member of the genus. The host factor requirements and receptors for entry of this class of viruses remain obscure. Using a Drosophila system, we identified the divalent metal ion transporter natural resistance-associated macrophage protein (NRAMP) as a host cell surface molecule required for Sindbis virus binding and entry into Drosophila cells. Consequently, flies mutant for dNRAMP were protected from virus infection. NRAMP2, the ubiquitously expressed vertebrate homolog, mediated binding and infection of Sindbi... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5140797 Wed, 17 Aug 2011 23:00:00 +0100 5140797 http://www.medworm.com/index.php?rid=5140796&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843868%26dopt%3DAbstract Authors: Burckhardt CJ, Suomalainen M, Schoenenberger P, Boucke K, Hemmi S, Greber UF Abstract Viral particle binding to plasma membrane receptors elicits virus motions, recruits signaling proteins, and triggers membrane bending and fission, finally resulting in endocytic virus uptake. Here we analyze how human adenovirus engages its receptor coxsackievirus adenovirus receptor (CAR) and coreceptor αv integrin to move on the plasma membrane. Virus binding to CAR through fiber knobs gave rise to diffusive motions and actomyosin-2-dependent drifts, while integrin-targeted viruses were spatially more confined. Diffusions, drifts, and confined motions were specifically observed with viral particles that were subsequently internalized. CAR-mediated drifts together with integrin binding ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5140796 Wed, 17 Aug 2011 23:00:00 +0100 5140796 http://www.medworm.com/index.php?rid=5140795&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843869%26dopt%3DAbstract We report the evolution of a transcription circuit in C. albicans that controls iron uptake and determines its fitness in both niches. Our analysis of DNA-binding proteins that regulate iron uptake by this organism suggests the evolutionary intercalation of a transcriptional activator called Sef1 between two broadly conserved iron-responsive transcriptional repressors, Sfu1 and Hap43. Sef1 activates iron-uptake genes and promotes virulence in a mouse model of bloodstream infection, whereas Sfu1 represses iron-uptake genes and is dispensable for virulence but promotes gastrointestinal commensalism. Thus, C. albicans can alternate between genetic programs conferring resistance to iron depletion in the bloodstream versus iron toxicity in the gut, and this may represent a fundamental attrib... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5140795 Wed, 17 Aug 2011 23:00:00 +0100 5140795 http://www.medworm.com/index.php?rid=5140794&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843870%26dopt%3DAbstract Authors: Schuijt TJ, Coumou J, Narasimhan S, Dai J, Deponte K, Wouters D, Brouwer M, Oei A, Roelofs JJ, van Dam AP, van der Poll T, Van't Veer C, Hovius JW, Fikrig E Abstract The Lyme disease agent Borrelia burgdorferi is primarily transmitted to vertebrates by Ixodes ticks. The classical and alternative complement pathways are important in Borrelia eradication by the vertebrate host. We recently identified a tick salivary protein, designated P8, which reduced complement-mediated killing of Borrelia. We now discover that P8 interferes with the human lectin complement cascade, resulting in impaired neutrophil phagocytosis and chemotaxis and diminished Borrelia lysis. Therefore, P8 was renamed the tick salivary lectin pathway inhibitor (TSLPI). TSLPI-silenced ticks, or ticks exposed ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5140794 Wed, 17 Aug 2011 23:00:00 +0100 5140794 http://www.medworm.com/index.php?rid=5140793&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843871%26dopt%3DAbstract Authors: Lannergård J, Gustafsson MC, Waldemarsson J, Norrby-Teglund A, Stålhammar-Carlemalm M, Lindahl G Abstract Sequence variation of antigenic proteins allows pathogens to evade antibody attack. The variable protein commonly includes a hypervariable region (HVR), which represents a key target for antibodies and is therefore predicted to be immunodominant. To understand the mechanism(s) of antibody evasion, we analyzed the clinically important HVR-containing M proteins of the human pathogen Streptococcus pyogenes. Antibodies elicited by M proteins were directed almost exclusively against the C-terminal part and not against the N-terminal HVR. Similar results were obtained for mice and humans with invasive S. pyogenes infection. Nevertheless, only anti-HVR antibodies protected... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5140793 Wed, 17 Aug 2011 23:00:00 +0100 5140793 http://www.medworm.com/index.php?rid=5140792&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843872%26dopt%3DAbstract We report that calprotectin enhances the sensitivity of Staphylococcus aureus to superoxide through inhibition of manganese-dependent bacterial superoxide defenses, thereby increasing superoxide levels within the bacterial cell. Superoxide dismutase activity is required for full virulence in a systemic model of S. aureus infection, and disruption of staphylococcal superoxide defenses by calprotectin augments the antimicrobial activity of neutrophils promoting in vivo clearance. Calprotectin mutated in two transition metal binding sites and therefore defective in binding manganese and zinc does not inhibit microbial growth, unequivocally linking the antimicrobial properties of calprotectin to metal chelation. These results suggest that calprotectin contributes to host defense by rendering... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5140792 Wed, 17 Aug 2011 23:00:00 +0100 5140792 http://www.medworm.com/index.php?rid=5140791&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843873%26dopt%3DAbstract Authors: Mandlik A, Livny J, Robins WP, Ritchie JM, Mekalanos JJ, Waldor MK Abstract Pathogens adapt to the host environment by altering their patterns of gene expression. Microarray-based and genetic techniques used to characterize bacterial gene expression during infection are limited in their ability to comprehensively and simultaneously monitor genome-wide transcription. We used massively parallel cDNA sequencing (RNA-seq) techniques to quantitatively catalog the transcriptome of the cholera pathogen, Vibrio cholerae, derived from two animal models of infection. Transcripts elevated in infected rabbits and mice relative to laboratory media derive from the major known V. cholerae virulence factors and also from genes and small RNAs not previously linked to virulence. The RNA-se... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5140791 Wed, 17 Aug 2011 23:00:00 +0100 5140791 http://www.medworm.com/index.php?rid=5049283&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767805%26dopt%3DAbstract Authors: Spiro S Nitric oxide (NO) is a poisonous free radical made by phagocytic cells to combat pathogens. Richardson et al. (2011) show that the Salmonella enterica serovar Typhimurium lipoamide dehydrogenase is a target for the nitrosative stress exerted by NO and related reactive nitrogen species. PMID: 21767805 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5049283 Wed, 20 Jul 2011 23:00:00 +0100 5049283 http://www.medworm.com/index.php?rid=5049281&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767806%26dopt%3DAbstract Authors: Spits H Innate lymphoid cells (ILCs) are novel players in innate immunity. Tumanov et al. (Tumanov et al., 2011) demonstrate that crosstalk between ILCs and dendritic cells involving membrane-bound lymphotoxin in ILCs and its receptor is critical for protection against colitogenic bacteria. PMID: 21767806 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5049281 Wed, 20 Jul 2011 23:00:00 +0100 5049281 http://www.medworm.com/index.php?rid=5049280&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767807%26dopt%3DAbstract Authors: Hofmann H, Pöhlmann S Lozach and colleagues show that phleboviruses (bunyaviridae), which comprise important emerging viral pathogens, exploit the C-type lectin DC-SIGN for dendritic cell binding, entry, and infection. The authors elegantly visualize the cellular processes underlying DC-SIGN-dependent viral capture and uptake. PMID: 21767807 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5049280 Wed, 20 Jul 2011 23:00:00 +0100 5049280 http://www.medworm.com/index.php?rid=5049277&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767808%26dopt%3DAbstract This study describes a remarkable mechanism by which a pathogen exploits host-cell machinery to properly target its virulence factors. PMID: 21767808 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5049277 Wed, 20 Jul 2011 23:00:00 +0100 5049277 http://www.medworm.com/index.php?rid=5049274&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767809%26dopt%3DAbstract We report that CPAF also targets chlamydial effectors secreted early during the establishment of the pathogen-containing vacuole ("inclusion"). We designed a cell-permeable CPAF-specific inhibitory peptide and used it to determine that CPAF prevents superinfection by degrading early Chlamydia effectors translocated during entry into a preinfected cell. Prolonged CPAF inhibition leads to loss of inclusion integrity and caspase-1-dependent death of infected epithelial cells. Thus, CPAF functions in niche protection, inclusion integrity and pathogen survival, making the development of CPAF-specific protease inhibitors an attractive antichlamydial therapeutic strategy. PMID: 21767809 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5049274 Wed, 20 Jul 2011 23:00:00 +0100 5049274 http://www.medworm.com/index.php?rid=5049272&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767810%26dopt%3DAbstract Authors: Richardson AR, Payne EC, Younger N, Karlinsey JE, Thomas VC, Becker LA, Navarre WW, Castor ME, Libby SJ, Fang FC Host nitric oxide (NO⋅) production is important for controlling intracellular bacterial pathogens, including Salmonella enterica serovar Typhimurium, but the underlying mechanisms are incompletely understood. S. Typhmurium 14028s is prototrophic for all amino acids but cannot synthesize methionine (M) or lysine (K) during nitrosative stress. Here, we show that NO⋅-induced MK auxotrophy results from reduced succinyl-CoA availability as a consequence of NO⋅ targeting of lipoamide-dependent lipoamide dehydrogenase (LpdA) activity. LpdA is an essential component of the pyruvate and α-ketoglutarate dehydrogenase complexes. Additional effects of NO⋅ on gene regul... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5049272 Wed, 20 Jul 2011 23:00:00 +0100 5049272 http://www.medworm.com/index.php?rid=5049269&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767811%26dopt%3DAbstract Authors: Tumanov AV, Koroleva EP, Guo X, Wang Y, Kruglov A, Nedospasov S, Fu YX Innate lymphoid cells (ILCs) have emerged as important players, regulating the balance between protective immunity and immunopathology at mucosal surfaces. However, mechanisms that regulate ILCs' effector functions during mucosal pathogenic challenge are poorly defined. Using mice infected with the natural mouse enteric pathogen Citrobacter rodentium, we demonstrate that lymphotoxin (LT) is essential for IL-22 production by intestinal ILCs. Blocking of LTβR signaling dramatically reduced intestinal IL-22 production after C. rodentium infection. Conversely, stimulating LTβR signaling induced an IL-22 protection pathway in LT-deficient mice. Furthermore, exogenous IL-22 expression rescued LTβR-deficient m... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5049269 Wed, 20 Jul 2011 23:00:00 +0100 5049269 http://www.medworm.com/index.php?rid=5049266&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767812%26dopt%3DAbstract Authors: Rowe JH, Ertelt JM, Aguilera MN, Farrar MA, Way SS Although pregnancy confers unique susceptibility to infection, the pregnancy-associated immune defects that erode host defense remain largely undefined. Herein, we demonstrate that expansion of immune-suppressive Foxp3(+) regulatory T cells (Tregs) which occurs physiologically during pregnancy or when experimentally induced in transgenic mice caused enhanced susceptibility to prenatal pathogens including Listeria and Salmonella species. Reciprocally, infection susceptibility was uniformly reduced with Treg ablation. Importantly however, the sustained expansion of maternal Tregs was essential for maintaining immune tolerance to the developing fetus because even partial transient ablation of Foxp3-expressing cells fractured mat... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5049266 Wed, 20 Jul 2011 23:00:00 +0100 5049266 http://www.medworm.com/index.php?rid=5049262&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767813%26dopt%3DAbstract Authors: Denard B, Seemann J, Chen Q, Gay A, Huang H, Chen Y, Ye J CREB3L1/OASIS is a cellular transcription factor synthesized as a membrane-bound precursor and activated by regulated intramembrane proteolysis in response to stimuli like ER stress. Comparing gene expression between Huh7 subclones that are permissive for hepatitis C virus (HCV) replication versus the nonpermissive parental Huh7 cells, we identified CREB3L1 as a host factor that inhibits proliferation of virus-infected cells. Upon infection with diverse DNA and RNA viruses, including murine γ-herpesvirus 68, HCV, West Nile virus (WNV), and Sendai virus, CREB3L1 was proteolytically cleaved, allowing its NH(2) terminus to enter the nucleus and induce multiple genes encoding inhibitors of the cell cycle to block cell prol... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5049262 Wed, 20 Jul 2011 23:00:00 +0100 5049262 http://www.medworm.com/index.php?rid=5049259&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767814%26dopt%3DAbstract Authors: Lozach PY, Kühbacher A, Meier R, Mancini R, Bitto D, Bouloy M, Helenius A During natural transmission, bunyaviruses are introduced into the skin through arthropod bites, and dermal dendritic cells (DCs) are the first to encounter incoming viruses. DC-SIGN is a C-type lectin highly expressed on the surface of dermal DCs. We found that several arthropod-borne phleboviruses (Bunyaviridae), including Rift Valley fever and Uukuniemi viruses, exploit DC-SIGN to infect DCs and other DC-SIGN-expressing cells. DC-SIGN binds the virus directly via interactions with high-mannose N-glycans on the viral glycoproteins and is required for virus internalization and infection. In live cells, virus-induced clustering of cell surface DC-SIGN could be visualized. An endocytosis-defective mutant... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=5049259 Wed, 20 Jul 2011 23:00:00 +0100 5049259 http://www.medworm.com/index.php?rid=4953657&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21669391%26dopt%3DAbstract Authors: Murray PJ In this issue of Cell Host & Microbe, Jensen et al. (2011) show that clonal lineages of Toxoplasma gondii have evolved distinct ways of subverting their favored host cell, the macrophage. The results suggest that T. gondii and the ROP kinases can be used to probe immune signaling pathways. PMID: 21669391 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4953657 Wed, 15 Jun 2011 23:00:00 +0100 4953657 http://www.medworm.com/index.php?rid=4953656&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21669392%26dopt%3DAbstract Authors: Figueiredo A, Hope TJ Integration of reverse transcribed HIV-1 DNA into the host genome, catalyzed by HIV-1 integrase, represents an obligate step in establishing productive viral infection. Allouch et al. (2011) identify KAP1 (TRIM28) as an interaction partner of acetylated integrase. KAP1, in complex with HDAC1, represses HIV-1 integration through specific deacetylation of HIV-1 integrase. PMID: 21669392 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4953656 Wed, 15 Jun 2011 23:00:00 +0100 4953656 http://www.medworm.com/index.php?rid=4953655&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21669393%26dopt%3DAbstract Authors: McCormick BA The type III secretion system-dependent epithelial invasion and dissemination of Shigella is stimulated by ATP released through hemichannels. Romero et al. (2011) show that prior to epithelial contact, Shigella is captured by nanometer-thin micropodial extensions at a distance from the cell surface, in a process involving ATP and connexin-mediated signaling. PMID: 21669393 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4953655 Wed, 15 Jun 2011 23:00:00 +0100 4953655 http://www.medworm.com/index.php?rid=4953654&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21669394%26dopt%3DAbstract Authors: Butler NS, Schmidt NW, Vaughan AM, Aly AS, Kappe SH, Harty JT While subunit vaccines have shown partial efficacy in clinical trials, radiation-attenuated sporozoites (RAS) remain the "gold standard" for sterilizing protection against Plasmodium infection in human vaccinees. The variability in immunogenicity and replication introduced by the extensive, random DNA damage necessary to generate RAS could be overcome by genetically attenuated parasites (GAP) designed via gene deletion to arrest at defined points during liver-stage development. Here, we demonstrate the principle that late liver stage-arresting GAP induce larger and broader CD8 T cell responses that provide superior protection in inbred and outbred mice compared to RAS or early-arresting GAP immunizations. Late live... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4953654 Wed, 15 Jun 2011 23:00:00 +0100 4953654 http://www.medworm.com/index.php?rid=4953653&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21669395%26dopt%3DAbstract Authors: Cortez M, Huynh C, Fernandes MC, Kennedy KA, Aderem A, Andrews NW Leishmania parasites infect macrophages, cells normally involved in innate defense against pathogens. Leishmania amazonensis and Leishmania major cause severe or mild disease, respectively, consistent with each parasite's ability to survive within activated macrophages. The mechanisms underlying increased virulence of L. amazonensis are mostly unknown. We show that L. amazonensis promotes its own survival by inducing expression of CD200, an immunoregulatory molecule that inhibits macrophage activation. L. amazonensis does not form typical nonhealing lesions in CD200(-/-) mice and cannot replicate in CD200(-/-) macrophages, an effect reversed by exogenous administration of soluble CD200-Fc. The less virulent L... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4953653 Wed, 15 Jun 2011 23:00:00 +0100 4953653 http://www.medworm.com/index.php?rid=4953652&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21669396%26dopt%3DAbstract Authors: Jensen KD, Wang Y, Wojno ED, Shastri AJ, Hu K, Cornel L, Boedec E, Ong YC, Chien YH, Hunter CA, Boothroyd JC, Saeij JP European and North American strains of the parasite Toxoplasma gondii belong to three distinct clonal lineages, type I, type II, and type III, which differ in virulence. Understanding the basis of Toxoplasma strain differences and how secreted effectors work to achieve chronic infection is a major goal of current research. Here we show that type I and III infected macrophages, a cell type required for host immunity to Toxoplasma, are alternatively activated, while type II infected macrophages are classically activated. The Toxoplasma rhoptry kinase ROP16, which activates STAT6, is responsible for alternative activation. The Toxoplasma dense granule protein GRA... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4953652 Wed, 15 Jun 2011 23:00:00 +0100 4953652 http://www.medworm.com/index.php?rid=4953651&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21669397%26dopt%3DAbstract This study identifies KAP1 as a cellular factor restricting HIV-1 infection and underscores the relevance of IN acetylation as a crucial step in the viral infectious cycle. PMID: 21669397 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4953651 Wed, 15 Jun 2011 23:00:00 +0100 4953651 http://www.medworm.com/index.php?rid=4953650&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21669398%26dopt%3DAbstract Authors: Kim YG, Park JH, Reimer T, Baker DP, Kawai T, Kumar H, Akira S, Wobus C, Núñez G Secondary bacterial infection is a common sequela to viral infection and is associated with increased lethality and morbidity. However, the underlying mechanisms remain poorly understood. We show that the TLR3/MDA5 agonist poly I:C or viral infection dramatically augments signaling via the NLRs Nod1 and Nod2 and enhances the production of proinflammatory cytokines. Enhanced Nod1 and Nod2 signaling by poly I:C required the TLR3/MDA5 adaptors TRIF and IPS-1 and was mediated by type I IFNs. Mechanistically, poly I:C or IFN-β induced the expression of Nod1, Nod2, and the Nod-signaling adaptor Rip2. Systemic administration of poly I:C or IFN-β or infection with murine norovirus-1 promoted inflamma... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4953650 Wed, 15 Jun 2011 23:00:00 +0100 4953650 http://www.medworm.com/index.php?rid=4953649&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21669399%26dopt%3DAbstract Authors: Romero S, Grompone G, Carayol N, Mounier J, Guadagnini S, Prevost MC, Sansonetti PJ, Tran Van Nhieu G Shigella, the causative agent of bacillary dysentery in humans, invades epithelial cells, using a type III secretory system (T3SS) to inject bacterial effectors into host cells and remodel the actin cytoskeleton. ATP released through connexin hemichanels on the epithelial membrane stimulates Shigella invasion and dissemination in epithelial cells. Here, we show that prior to contact with the cell body, Shigella is captured by nanometer-thin micropodial extensions (NMEs) at a distance from the cell surface, in a process involving the T3SS tip complex proteins and stimulated by ATP- and connexin-mediated signaling. Upon bacterial contact, NMEs retract, bringing bacteria in cont... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4953649 Wed, 15 Jun 2011 23:00:00 +0100 4953649 http://www.medworm.com/index.php?rid=4953648&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21669400%26dopt%3DAbstract Authors: Tegtmeyer N, Wittelsberger R, Hartig R, Wessler S, Martinez-Quiles N, Backert S Cell migration and invasion require the coordinated regulation of cytoskeletal architectural changes by signaling factors, including the actin-binding protein cortactin. Bacterial and viral pathogens subvert these signaling factors to promote their uptake, spread and dissemination. We show that the gastric pathogen Helicobacter pylori (Hp) targets cortactin by two independent processes leading to its tyrosine dephosphorylation and serine phosphorylation to regulate cell scattering and elongation. The phosphorylation status of cortactin dictates its subcellular localization and signaling partners. Upon infection, cortactin was found to interact with and stimulate the kinase activity of focal adhesio... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4953648 Wed, 15 Jun 2011 23:00:00 +0100 4953648 http://www.medworm.com/index.php?rid=4855502&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21575903%26dopt%3DAbstract Authors: Nathan C The dwindling supply of effective treatments for infectious disease is cause for alarm. Searches for anti-infectives yielding fewer and fewer novel discoveries have been concentrated in overly restricted regions of target space, screening space, chemical space, and competition space. Appreciating the diverse axes of these spaces may encourage wider exploration. PMID: 21575903 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4855502 Wed, 18 May 2011 23:00:00 +0100 4855502 http://www.medworm.com/index.php?rid=4855501&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21575904%26dopt%3DAbstract Authors: Tareen SU, Emerman M Retroviral capsids can be recognized and degraded by a host protein, Trim5α. A recent study in Nature (Pertel et al., 2011) shows that, upon sensing of the retrovirus capsid lattice, Trim5α generates free ubiquitin chains that activate the TAK1 kinase and downstream innate immune response genes. PMID: 21575904 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4855501 Wed, 18 May 2011 23:00:00 +0100 4855501 http://www.medworm.com/index.php?rid=4855500&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21575905%26dopt%3DAbstract Authors: Unterholzner L, Bowie AG It has been assumed that cells distinguish viral from cellular DNA due to the former's presence in the cytosol. However, in this issue, Kerur et al. (2011) propose that the DNA genome of Kaposi's sarcoma-associated herpesvirus (KSHV) is recognized inside the nucleus by the DNA sensor IFI16, leading inflammasome activation. PMID: 21575905 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4855500 Wed, 18 May 2011 23:00:00 +0100 4855500 http://www.medworm.com/index.php?rid=4855499&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21575906%26dopt%3DAbstract This study showcases the use of a non-germ-free mouse model to identify specific members of the microbiota involved in disease development. PMID: 21575906 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4855499 Wed, 18 May 2011 23:00:00 +0100 4855499 http://www.medworm.com/index.php?rid=4855498&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21575907%26dopt%3DAbstract Authors: Netea MG, Quintin J, van der Meer JW Immune responses in vertebrates are classically divided into innate and adaptive, with only the latter being able to build up immunological memory. However, although lacking adaptive immune responses, plants and invertebrates are protected against reinfection with pathogens, and invertebrates even display transplant rejection. In mammals, past "forgotten" studies demonstrate cross-protection between infections independently of T and B cells, and more recently memory properties for NK cells and macrophages, prototypical cells of innate immunity, have been described. We now posit that mammalian innate immunity also exhibits an immunological memory of past insults, for which we propose the term "trained immunity." Understanding trained immunit... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4855498 Wed, 18 May 2011 23:00:00 +0100 4855498 http://www.medworm.com/index.php?rid=4855497&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21575908%26dopt%3DAbstract Authors: Kerur N, Veettil MV, Sharma-Walia N, Bottero V, Sadagopan S, Otageri P, Chandran B Inflammasomes are cytoplasmic sensors of foreign molecules, including pathogens, and function to induce caspase-1 activation and IL-1β cytokine maturation. Whether such a mechanism exists in the nucleus and is effective against nuclear replicating pathogens is unknown. Nuclear replicating herpesvirus KSHV is associated with Kaposi Sarcoma, an angioproliferative tumor characterized by an inflammatory microenvironment including IL-1β. We demonstrate that during KSHV infection of endothelial cells, interferon gamma-inducible protein 16 (IFI16) interacts with the adaptor molecule ASC and procaspase-1 to form a functional inflammasome. This complex was initially detected in the nucleus and subsequ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4855497 Wed, 18 May 2011 23:00:00 +0100 4855497 http://www.medworm.com/index.php?rid=4855496&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21575909%26dopt%3DAbstract In this study we identified a highly conserved Tectonin domain-containing protein, Tecpr1, as an Atg5 binding partner that colocalized with Atg5 at Shigella-containing phagophores. Tecpr1 activity is necessary for efficient autophagic targeting of bacteria, but has no effect on rapamycin- or starvation-induced canonical autophagy. Tecpr1 interacts with WIPI-2, a yeast Atg18 homolog and PI(3)P-interacting protein required for phagophore formation, and they colocalize to phagophores. Although Tecpr1-deficient mice appear normal, Tecpr1-deficient MEFs were defective for selective autophagy and supported increased intracellular multiplication of Shigella. Further, depolarized mitochondria and misfolded protein aggregates accumulated in the Tecpr1-knockout MEFs. Thus, we identify a Tecpr1-depen... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4855496 Wed, 18 May 2011 23:00:00 +0100 4855496 http://www.medworm.com/index.php?rid=4855495&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21575910%26dopt%3DAbstract Authors: Bloom SM, Bijanki VN, Nava GM, Sun L, Malvin NP, Donermeyer DL, Dunne WM, Allen PM, Stappenbeck TS The intestinal microbiota is important for induction of inflammatory bowel disease (IBD). IBD is associated with complex shifts in microbiota composition, but it is unclear whether specific bacterial subsets induce IBD and, if so, whether their proportions in the microbiota are altered during disease. Here, we fulfilled Koch's postulates in host-genotype-specific fashion using a mouse model of IBD with human-relevant disease-susceptibility mutations. From screening experiments we isolated common commensal Bacteroides species, introduced them into antibiotic-pretreated mice, and quantitatively reisolated them in culture. The bacteria colonized IBD-susceptible and -nonsusceptible m... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4855495 Wed, 18 May 2011 23:00:00 +0100 4855495 http://www.medworm.com/index.php?rid=4855494&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21575911%26dopt%3DAbstract Authors: Clarke TB, Francella N, Huegel A, Weiser JN Streptococcus pneumoniae and Haemophilus influenzae are members of the normal human nasal microbiota with the ability to cause invasive infections. Bacterial invasion requires translocation across the epithelium; however, mechanistic understanding of this process is limited. Examining the epithelial response to murine colonization by S. pneumoniae and H. influenzae, we observed the TLR-dependent downregulation of claudins 7 and 10, tight junction components key to the maintenance of epithelial barrier integrity. When modeled in vitro, claudin downregulation was preceded by upregulation of SNAIL1, a transcriptional repressor of tight junction components, and these phenomena required p38 MAPK and TGF-β signaling. Consequently, down... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4855494 Wed, 18 May 2011 23:00:00 +0100 4855494 http://www.medworm.com/index.php?rid=4855493&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21575912%26dopt%3DAbstract We examined the interactions of pDCs with hyphae of the invasive human fungal pathogen Aspergillus fumigatus. Human pDCs spread over hyphae and inhibited their growth. Antifungal activity was retained in pDC lysates, did not require direct fungal contact, and was partially reversed by zinc. Incubation with hyphae resulted in pDC cytotoxicity, partly due to fungal gliotoxin secretion. Following hyphal stimulation, pDCs released proinflammatory cytokines via a TLR9-independent mechanism. Pulmonary challenge of mice with A. fumigatus resulted in a substantial influx of pDCs into lungs, and pDC-depleted mice were hypersusceptible to invasive aspergillosis. These data demonstrate the antifungal activity of pDCs against A. fumigatus and establish their nonredundant role in host defenses agains... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4855493 Wed, 18 May 2011 23:00:00 +0100 4855493 http://www.medworm.com/index.php?rid=4855492&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21575913%26dopt%3DAbstract Authors: Dierking K, Polanowska J, Omi S, Engelmann I, Gut M, Lembo F, Ewbank JJ, Pujol N The cuticle and epidermis of Caenorhabditis elegans provide the first line of defense against invading pathogens. Upon invasion by the fungal pathogen Drechmeria coniospora, C. elegans responds by upregulating the expression of antimicrobial peptides (AMPs) in the epidermis via activation of at least two pathways, a neuroendocrine TGF-β pathway and a p38 MAPK pathway. Here, we identify the sodium-neurotransmitter symporter SNF-12, a member of the solute carrier family (SLC6), as being essential for both these immune signaling pathways. We also identify the STAT transcription factor-like protein STA-2 as a direct physical interactor of SNF-12 and show that the two proteins function together to re... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4855492 Wed, 18 May 2011 23:00:00 +0100 4855492 http://www.medworm.com/index.php?rid=4855491&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21575914%26dopt%3DAbstract Authors: da Glória Sousa M, Reid DM, Schweighoffer E, Tybulewicz V, Ruland J, Langhorne J, Yamasaki S, Taylor PR, Almeida SR, Brown GD Chromoblastomycosis is a chronic skin infection caused by the fungus Fonsecaea pedrosoi. Exploring the reasons underlying the chronic nature of F. pedrosoi infection in a murine model of chromoblastomycosis, we find that chronicity develops due to a lack of pattern recognition receptor (PRR) costimulation. F. pedrosoi was recognized primarily by C-type lectin receptors (CLRs), but not by Toll-like receptors (TLRs), which resulted in the defective induction of proinflammatory cytokines. Inflammatory responses to F. pedrosoi could be reinstated by TLR costimulation, but also required the CLR Mincle and signaling via the Syk/CARD9 pathway. Importantly,... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4855491 Wed, 18 May 2011 23:00:00 +0100 4855491 http://www.medworm.com/index.php?rid=4802498&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21501822%26dopt%3DAbstract Authors: Telford JL, Baldari CT Using a syringe-like device, Shigella delivers an array of virulence factors into host cells to facilitate bacterial colonization and disable the host's innate immune defense. In this issue of Cell Host & Microbe, Konradt and colleagues (Konradt et al., 2011) show that Shigella also subverts adaptive immunity by targeting T cells through a mechanism involving PIP(2) breakdown. PMID: 21501822 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4802498 Wed, 20 Apr 2011 23:00:00 +0100 4802498 http://www.medworm.com/index.php?rid=4802497&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21501823%26dopt%3DAbstract Authors: Mercer J In the evolutionary battle between virus and host, viruses have developed numerous strategies to subjugate indispensable cellular functions. In this issue of Cell Host & Microbe, Morizono and colleagues (Morizono et al., 2011) describe how viruses hijack host apoptotic clearance machinery for entry. A host factor called Gas6 enhances infection by bridging virus phosphatidylserine to the clearance receptor Axl. PMID: 21501823 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4802497 Wed, 20 Apr 2011 23:00:00 +0100 4802497 http://www.medworm.com/index.php?rid=4802496&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21501824%26dopt%3DAbstract This study pioneers the observation that Leishmania parasites metabolically paralyze their host cells using an elegant translation shutoff mechanism. PMID: 21501824 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4802496 Wed, 20 Apr 2011 23:00:00 +0100 4802496 http://www.medworm.com/index.php?rid=4802495&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21501825%26dopt%3DAbstract Authors: Wainberg MA, Jeang KT Xenotropic murine leukemia virus-related virus (XMRV) has been proposed to be associated with prostate cancer and chronic fatigue syndrome (CFS). This proposition has been controversial because many investigators have failed to replicate the reported associations. Here, we explore whether XMRV is an authentic human pathogen in the light of recent findings that indicate otherwise. PMID: 21501825 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4802495 Wed, 20 Apr 2011 23:00:00 +0100 4802495 http://www.medworm.com/index.php?rid=4802494&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21501826%26dopt%3DAbstract Authors: Konradt C, Frigimelica E, Nothelfer K, Puhar A, Salgado-Pabon W, di Bartolo V, Scott-Algara D, Rodrigues CD, Sansonetti PJ, Phalipon A Shigella, the Gram-negative enteroinvasive bacterium that causes shigellosis, relies on its type III secretion system (TTSS) and injected effectors to modulate host cell functions. However, consequences of the interaction between Shigella and lymphocytes have not been investigated. We show that Shigella invades activated human CD4(+) T lymphocytes. Invasion requires a functional TTSS and results in inhibition of chemokine-induced T cell migration, an effect mediated by the TTSS effector IpgD, a phosphoinositide 4-phosphatase. Remarkably, IpgD injection into bystander T cells can occur in the absence of cell invasion. Upon IpgD-mediated hydrol... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4802494 Wed, 20 Apr 2011 23:00:00 +0100 4802494 http://www.medworm.com/index.php?rid=4802493&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21501827%26dopt%3DAbstract Authors: Hänisch J, Kölm R, Wozniczka M, Bumann D, Rottner K, Stradal TE Salmonella stimulates host cell invasion using virulence effectors translocated by the pathogen's type-three secretion system (T3SS). These factors manipulate host signaling pathways, primarily driven by Rho family GTPases, which culminates in Arp2/3 complex-dependent activation of host actin nucleation to mediate the uptake of Salmonella into host cells. However, recent data argue for the existence of additional mechanisms that cooperate in T3SS-dependent Salmonella invasion. We identify a myosin II-mediated mechanism, operating independent of but complementary to the Arp2/3-dependent pathway, as contributing to Salmonella invasion into nonphagocytic cells. We also establish that the T3SS effector SopB constitu... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4802493 Wed, 20 Apr 2011 23:00:00 +0100 4802493 http://www.medworm.com/index.php?rid=4802492&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21501828%26dopt%3DAbstract Authors: Morizono K, Xie Y, Olafsen T, Lee B, Dasgupta A, Wu AM, Chen IS Virus entry into cells is typically initiated by binding of virally encoded envelope proteins to specific cell surface receptors. Studying infectivity of lentivirus pseudotypes lacking envelope binding, we still observed high infectivity for some cell types. On further investigation, we discovered that this infectivity is conferred by the soluble bovine protein S in fetal calf serum, or Gas6, its human homolog. Gas6 enhances native infectivity of pseudotypes of multiple viral envelope proteins. Gas6 mediates binding of the virus to target cells by bridging virion envelope phosphatidylserine to Axl, a TAM receptor tyrosine kinase on target cells. Phagocytic clearance of apoptotic cells is known to involve bridging ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4802492 Wed, 20 Apr 2011 23:00:00 +0100 4802492 http://www.medworm.com/index.php?rid=4802491&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21501829%26dopt%3DAbstract Authors: Kok KH, Lui PY, Ng MH, Siu KL, Au SW, Jin DY RIG-I, a virus sensor that triggers innate antiviral response, is a DExD/H box RNA helicase bearing structural similarity with Dicer, an RNase III-type nuclease that mediates RNA interference. Dicer requires double-stranded RNA-binding protein partners, such as PACT, for optimal activity. Here we show that PACT physically binds to the C-terminal repression domain of RIG-I and potently stimulates RIG-I-induced type I interferon production. PACT potentiates the activation of RIG-I by poly(I:C) of intermediate length. PACT also cooperates with RIG-I to sustain the activation of antiviral defense. Depletion of PACT substantially attenuates viral induction of interferons. The activation of RIG-I by PACT does not require double-stranded R... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4802491 Wed, 20 Apr 2011 23:00:00 +0100 4802491 http://www.medworm.com/index.php?rid=4802490&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21501830%26dopt%3DAbstract Authors: Macgregor P, Savill NJ, Hall D, Matthews KR Sleeping sickness is characterized by waves of the extracellular parasite Trypanosoma brucei in host blood, with infections continuing for months or years until inevitable host death. These waves reflect the dynamic conflict between the outgrowth of a succession of parasite antigenic variants and their control by the host immune system. Although a contributor to these dynamics is the density-dependent differentiation from proliferative "slender forms" to transmissible "stumpy forms," an absence of markers discriminating stumpy forms has prevented accurate parameterization of this component. Here, we exploit the stumpy-specific PAD1 marker, which functionally defines transmission competence, to quantitatively monitor stumpy formation ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4802490 Wed, 20 Apr 2011 23:00:00 +0100 4802490 http://www.medworm.com/index.php?rid=4802489&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21501831%26dopt%3DAbstract Authors: Forestier CL, Machu C, Loussert C, Pescher P, Späth GF Leishmania donovani causes human visceral leishmaniasis. The parasite infectious cycle comprises extracellular flagellated promastigotes that proliferate inside the insect vector, and intracellular nonmotile amastigotes that multiply within infected host cells. Using primary macrophages infected with virulent metacyclic promastigotes and high spatiotemporal resolution microscopy, we dissect the dynamics of the early infection process. We find that motile promastigotes enter macrophages in a polarized manner through their flagellar tip and are engulfed into host lysosomal compartments. Persistent intracellular flagellar activity leads to reorientation of the parasite flagellum toward the host cell periphery and results in ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4802489 Wed, 20 Apr 2011 23:00:00 +0100 4802489 http://www.medworm.com/index.php?rid=4802488&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21501832%26dopt%3DAbstract This study demonstrates that Leishmania evolved a survival mechanism by activating 4E-BPs, which serve as major targets for host translational control. PMID: 21501832 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4802488 Wed, 20 Apr 2011 23:00:00 +0100 4802488 http://www.medworm.com/index.php?rid=4637761&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21396898%26dopt%3DAbstract Authors: Morita E, Sandrin V, McCullough J, Katsuyama A, Baci Hamilton I, Sundquist WI Two early-acting components of the cellular ESCRT pathway, ESCRT-I and ALIX, participate directly in HIV-1 budding. The membrane fission activities of ESCRT-III subunits are also presumably required, but humans express 11 different CHMP/ESCRT-III proteins whose functional contributions are not yet clear. We therefore depleted cells of each of the different CHMP proteins and protein families and examined the effects on HIV-1 budding. Virus release was profoundly inhibited by codepletion of either CHMP2 or CHMP4 family members, resulting in ≥100-fold titer reductions. CHMP2A and CHMP4B proteins bound one another, and this interaction was required for budding. By contrast, virus release was reduced on... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4637761 Thu, 17 Mar 2011 00:00:00 +0100 4637761 http://www.medworm.com/index.php?rid=4637760&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402352%26dopt%3DAbstract Authors: Keestra AM, Bäumler AJ Salmonella survives in macrophages by using a molecular syringe to deliver proteins into the host-cell cytosol where they manipulate phagocyte physiology. Arpaia and colleagues (Arpaia et al., 2011) show that deployment of this virulence factor is triggered by the very responses that are intended to confer host resistance. PMID: 21402352 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4637760 Thu, 17 Mar 2011 00:00:00 +0100 4637760 http://www.medworm.com/index.php?rid=4637759&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402353%26dopt%3DAbstract Authors: Bent A Many effectors secreted by pathogenic bacteria suppress host signal transduction pathways that activate host defense responses. In this issue of Cell Host & Microbe, Zhou et al. (2011) now broaden that theme by demonstrating that HopZ1b from Pseudomonas syringae pv. glycinea causes degradation of a host enzyme directly involved in the synthesis of antimicrobial phytoalexin compounds. PMID: 21402353 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4637759 Thu, 17 Mar 2011 00:00:00 +0100 4637759 http://www.medworm.com/index.php?rid=4637758&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402354%26dopt%3DAbstract Authors: Trono D, Marzetta F The early establishment of a reservoir of latently infected T cells is a sobering obstacle to HIV eradication, in spite of the efficacy of current antiretroviral therapies. That latent proviruses might also hide in multipotent hematopoietic stem cells suggests an even more formidable challenge and potentially has therapeutic implications. PMID: 21402354 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4637758 Thu, 17 Mar 2011 00:00:00 +0100 4637758 http://www.medworm.com/index.php?rid=4637757&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402355%26dopt%3DAbstract Authors: Weissenhorn W, Göttlinger H HIV-1 engages the cellular ESCRT-III/VPS4 membrane scission machinery for its escape from host cells. Three papers now begin to demystify its mode of action by showing that HIV-1 requires only the transient recruitment of a surprisingly small subset of ESCRT-III components, whose membrane abscission function depends on VPS4 activity. PMID: 21402355 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4637757 Thu, 17 Mar 2011 00:00:00 +0100 4637757 http://www.medworm.com/index.php?rid=4637756&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402356%26dopt%3DAbstract Authors: Hull CM While a polysaccharide capsule is known to be important for preventing phagocytosis of the human pathogen Cryptococcus neoformans, other antiphagocytic pathways have been generally elusive. Now, a capsule-independent pathway has been identified that prevents macrophages from ingesting the fungus, contributing to evasion of the host immune response. PMID: 21402356 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4637756 Thu, 17 Mar 2011 00:00:00 +0100 4637756 http://www.medworm.com/index.php?rid=4637755&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402357%26dopt%3DAbstract Authors: Zhou H, Lin J, Johnson A, Morgan RL, Zhong W, Ma W Type III secreted effectors (T3SEs), such as Pseudomonas syringae HopZ1, are essential bacterial virulence proteins injected into the host cytosol to facilitate infection. However, few direct targets of T3SEs are known. Investigating the target(s) of HopZ1 in soybean, a natural P. syringae host, we find that HopZ1 physically interacts with the isoflavone biosynthesis enzyme, 2-hydroxyisoflavanone dehydratase (GmHID1). P. syringae infection induces gmhid1 expression and production of daidzein, a major soybean isoflavone. Silencing gmhid1 increases susceptibility to P. syringae infection, supporting a role for GmHID1 in innate immunity. P. syringae expressing active but not the catalytic mutant of HopZ1 inhibits daidzein induc... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4637755 Thu, 17 Mar 2011 00:00:00 +0100 4637755 http://www.medworm.com/index.php?rid=4637754&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402358%26dopt%3DAbstract We report the crystal structure of an MLA receptor's invariant CC domain, which reveals a rod-shaped homodimer. MLA receptors also self-associate in vivo, but self-association appears to be independent of effector-triggered receptor activation. MLA CC mutants that fail to self-interact impair in planta cell death activity triggered by the CC domain alone and by an autoactive full-length MLA receptor that mimics its ATP-bound state. Thus, CC domain-dependent dimerization of the immune sensor defines a minimal functional unit and implies a role for the dimeric CC module in downstream immune signaling. PMID: 21402358 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4637754 Thu, 17 Mar 2011 00:00:00 +0100 4637754 http://www.medworm.com/index.php?rid=4637753&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402359%26dopt%3DAbstract Authors: Bernoux M, Ve T, Williams S, Warren C, Hatters D, Valkov E, Zhang X, Ellis JG, Kobe B, Dodds PN The Toll/interleukin-1 receptor (TIR) domain occurs in animal and plant immune receptors. In the animal Toll-like receptors, homodimerization of the intracellular TIR domain is required for initiation of signaling cascades leading to innate immunity. By contrast, the role of the TIR domain in cytoplasmic nucleotide-binding/leucine-rich repeat (NB-LRR) plant immune resistance proteins is poorly understood. L6 is a TIR-NB-LRR resistance protein from flax (Linum usitatissimum) that confers resistance to the flax rust phytopathogenic fungus (Melampsora lini). We determine the crystal structure of the L6 TIR domain and show that, although dispensable for pathogenic effector protein recog... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4637753 Thu, 17 Mar 2011 00:00:00 +0100 4637753 http://www.medworm.com/index.php?rid=4637752&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402360%26dopt%3DAbstract Authors: Popkin DL, Teijaro JR, Sullivan BM, Urata S, Rutschmann S, de la Torre JC, Kunz S, Beutler B, Oldstone M The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), which naturally persists in rodents, represents a model for HIV, HBV, and HCV. Cleavage of the viral glycoprotein precursor by membrane-bound transcription factor peptidase, site 1 (Mbtps1 or site-1 protease), is crucial for the life cycle of arenaviruses and therefore represents a potential target for therapy. Recently, we reported a viable hypomorphic allele of Mbtps1 (woodrat) encoding a protease with diminished enzymatic activity. Using the woodrat allele, we examine the role of Mbtps1 during persistent LCMV infection. Surprisingly, Mbtps1 inhibition limits persistent but not acute viral infection and ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4637752 Thu, 17 Mar 2011 00:00:00 +0100 4637752 http://www.medworm.com/index.php?rid=4637751&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402361%26dopt%3DAbstract Authors: Carter CC, McNamara LA, Onafuwa-Nuga A, Shackleton M, Riddell J, Bixby D, Savona MR, Morrison SJ, Collins KL HIV infection is characterized by gradual immune system collapse and hematopoietic dysfunction. We recently showed that HIV enters multipotent hematopoietic progenitor cells and establishes both active cytotoxic and latent infections that can be reactivated by myeloid differentiation. However, whether these multipotent progenitors include long-lived hematopoietic stem cells (HSCs) that could establish viral reservoirs for the life of the infected person remains unknown. Here we provide direct evidence that HIV targets long-lived HSCs and show that infected HSCs yield stable, multilineage engraftment in a xenograft model. Furthermore, we establish that the capacity to us... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4637751 Thu, 17 Mar 2011 00:00:00 +0100 4637751 http://www.medworm.com/index.php?rid=4637750&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402362%26dopt%3DAbstract Authors: Chun CD, Brown JC, Madhani HD The antiphagocytic polysaccharide capsule of the human fungal pathogen Cryptococcus neoformans is a major virulence attribute. However, previous studies of the pleiotropic virulence determinant Gat201, a GATA family transcription factor, suggested that capsule-independent antiphagocytic mechanisms exist. We have determined that Gat201 controls the mRNA levels of ∼1100 genes (16% of the genome) and binds the upstream regions of ∼130 genes. Seven Gat201-bound genes encode for putative and known transcription factors-including two previously implicated in virulence-suggesting an extensive regulatory network. Systematic analysis pinpointed two critical Gat201-bound genes, GAT204 (a transcription factor) and BLP1, which account for much of the caps... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4637750 Thu, 17 Mar 2011 00:00:00 +0100 4637750 http://www.medworm.com/index.php?rid=4524677&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21320688%26dopt%3DAbstract Authors: Kunisawa J, Kiyono H Quantitative and qualitative aspects of commensal bacteria determine the active and quiescent status of host immunity. In a recent Science paper, Atarashi et al. (2011) identify Clostridium clusters IV and XIVa as indigenous commensal bacteria that induce regulatory T cells for the creation and maintenance of immunological homeostasis. PMID: 21320688 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4524677 Thu, 17 Feb 2011 00:00:00 +0100 4524677 http://www.medworm.com/index.php?rid=4524676&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21320689%26dopt%3DAbstract Authors: Kamil JP, Coen DM Mutations in the human cytomegalovirus UL27 gene confer resistance to an inhibitor of the viral protein kinase UL97. Reitsma and colleagues (2011) demonstrate that UL27 destabilizes the Tip60 histone acetyltransferase, setting forth intriguing new mechanisms for antiviral drug resistance and for viral regulation of the cell cycle. PMID: 21320689 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4524676 Thu, 17 Feb 2011 00:00:00 +0100 4524676 http://www.medworm.com/index.php?rid=4524675&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21320690%26dopt%3DAbstract Authors: Innes RW Pioneering plant research has shown that many Nod-like receptors (NLRs) detect pathogens indirectly via recognizing modifications of other host proteins. In this issue, two groups show that the RPM1 NLR is activated by phosphorylation of the host protein RIN4, probably resulting from activation of a host kinase by pathogen effectors. PMID: 21320690 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4524675 Thu, 17 Feb 2011 00:00:00 +0100 4524675 http://www.medworm.com/index.php?rid=4524674&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21320691%26dopt%3DAbstract Authors: Paton JC, Ogunniyi AD Nasopharyngeal colonization by Streptococcus pneumoniae precedes invasive disease and mediates community transmission of the pathogen. In this issue, Moffitt et al. (2011) used proteomic analysis to identify conserved pneumococcal protein vaccine antigens that elicit T(H)17-dependent responses capable of preventing such colonization. PMID: 21320691 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4524674 Thu, 17 Feb 2011 00:00:00 +0100 4524674 http://www.medworm.com/index.php?rid=4524673&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21320692%26dopt%3DAbstract Authors: Bauman Y, Nachmani D, Vitenshtein A, Tsukerman P, Drayman N, Stern-Ginossar N, Lankry D, Gruda R, Mandelboim O The human polyoma viruses JCV and BKV establish asymptomatic persistent infection in 65%-90% of humans but can cause severe illness under immunosuppressive conditions. The mechanisms by which these viruses evade immune recognition are unknown. Here we show that a viral miRNA identical in sequence between JCV and BKV targets the stress-induced ligand ULBP3, which is a protein recognized by the killer receptor NKG2D. Consequently, viral miRNA-mediated ULBP3 downregulation results in reduced NKG2D-mediated killing of virus-infected cells by natural killer (NK) cells. Importantly, when the activity of the viral miRNA was inhibited during infection, NK cells killed the inf... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4524673 Thu, 17 Feb 2011 00:00:00 +0100 4524673 http://www.medworm.com/index.php?rid=4524672&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21320693%26dopt%3DAbstract Authors: Reitsma JM, Savaryn JP, Faust K, Sato H, Halligan BD, Terhune SS Infection with the β-herpesvirus human cytomegalovirus (HCMV) is lifelong, causing limited disease in healthy adults, but life threatening in immunocompromised individuals. The viral kinase pUL97, a functional ortholog of cellular cyclin-dependent kinases (CDKs), is critical for HCMV replication and a target for antiviral drug development. Upon kinase inhibition, drug-resistant strains emerge with mutations in UL27, an HCMV gene of unknown function. Using a proteomics approach, we discovered that pUL27 is necessary and sufficient to degrade Tip60, a host acetyltransferase and interacting partner of HIV Tat. Consistent with this, the expression of Tat restored antiviral inhibition of an otherwise resistant HCMV ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4524672 Thu, 17 Feb 2011 00:00:00 +0100 4524672 http://www.medworm.com/index.php?rid=4524671&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21320694%26dopt%3DAbstract Authors: Song J, Durrant WE, Wang S, Yan S, Tan EH, Dong X Systemic acquired resistance (SAR), an inducible plant-defense response to local infection, requires the signaling molecule salicylic acid (SA) and the transcriptional coactivator NPR1, with concerted activation of pathogenesis-related (PR) genes. Arabidopsis sni1 is an npr1 suppressor and derepression of defense genes in sni1 causes reduced growth and fertility and increased homologous recombination. Characterizing suppressors of sni1, we identify the DNA damage repair proteins SSN2 and RAD51D as genetic and physical interactors with SNI1. During plant defense, SSN2 and possibly RAD51D replace the transcription repressor SNI1 at pathogenesis-related gene promoters. In the presence of SNI1, NPR1 is also required for SSN2 bindin... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4524671 Thu, 17 Feb 2011 00:00:00 +0100 4524671 http://www.medworm.com/index.php?rid=4524670&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21320695%26dopt%3DAbstract Authors: Chung EH, da Cunha L, Wu AJ, Gao Z, Cherkis K, Afzal AJ, Mackey D, Dangl JL The Arabidopsis NB-LRR immune receptor RPM1 recognizes the Pseudomonas syringae type III effectors AvrB or AvrRpm1 to mount an immune response. Although neither effector is itself a kinase, AvrRpm1 and AvrB are known to target Arabidopsis RIN4, a negative regulator of basal plant defense, for phosphorylation. We show that RIN4 phosphorylation activates RPM1. RIN4(142-176) is necessary and, with appropriate localization sequences, sufficient to support effector-triggered RPM1 activation, with the threonine residue at position 166 being critical. Phosphomimic substitutions at T166 cause effector-independent RPM1 activation. RIN4 T166 is phosphorylated in vivo in the presence of AvrB or AvrRpm1. RIN4 mut... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4524670 Thu, 17 Feb 2011 00:00:00 +0100 4524670 http://www.medworm.com/index.php?rid=4524669&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21320696%26dopt%3DAbstract Authors: Liu J, Elmore JM, Lin ZJ, Coaker G Plants have evolved sophisticated surveillance systems to recognize pathogen effectors delivered into host cells. RPM1 is an NB-LRR immune receptor that recognizes the Pseudomonas syringae effectors AvrB and AvrRpm1. Both effectors associate with and affect the phosphorylation of RIN4, an immune regulator. Although the kinase and the specific mechanisms involved are unclear, it has been hypothesized that RPM1 recognizes phosphorylated RIN4. Here, we identify RIPK as a RIN4-interacting receptor-like protein kinase that phosphorylates RIN4. In response to bacterial effectors, RIPK phosphorylates RIN4 at amino acid residues T21, S160, and T166. RIN4 phosphomimetic mutants display constitutive activation of RPM1-mediated defense responses and RIN... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4524669 Thu, 17 Feb 2011 00:00:00 +0100 4524669 http://www.medworm.com/index.php?rid=4524668&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21320697%26dopt%3DAbstract Authors: Los FC, Kao CY, Smitham J, McDonald KL, Ha C, Peixoto CA, Aroian RV Pore-forming toxins (PFTs) secreted by pathogenic bacteria are the most common bacterial protein toxins and are important virulence factors for infection. PFTs punch holes in host cell plasma membranes, and although cells can counteract the resulting membrane damage, the underlying mechanisms at play remain unclear. Using Caenorhabditis elegans as a model, we demonstrate in vivo and in an intact epithelium that intestinal cells respond to PFTs by increasing levels of endocytosis, dependent upon RAB-5 and RAB-11, which are master regulators of endocytic and exocytic events. Furthermore, we find that RAB-5 and RAB-11 are required for protection against PFT and to restore integrity to the plasma membrane. One ph... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4524668 Thu, 17 Feb 2011 00:00:00 +0100 4524668 http://www.medworm.com/index.php?rid=4524667&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21320698%26dopt%3DAbstract Authors: Moffitt KL, Gierahn TM, Lu YJ, Gouveia P, Alderson M, Flechtner JB, Higgins DE, Malley R Streptococcus pneumoniae is a leading cause of mortality in young children. While successful conjugate polysaccharide vaccines exist, a less expensive serotype-independent protein-based pneumococcal vaccine offers a major advancement for preventing life-threatening pneumococcal infections, particularly in developing nations. IL-17A-secreting CD4+ T cells (T(H)17) mediate resistance to mucosal colonization by multiple pathogens including S. pneumoniae. Screening an expression library containing >96% of predicted pneumococcal proteins, we identified antigens recognized by T(H)17 cells from mice immune to pneumococcal colonization. The identified antigens also elicited IL-17A secretion fr... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4524667 Thu, 17 Feb 2011 00:00:00 +0100 4524667 http://www.medworm.com/index.php?rid=4399948&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21238940%26dopt%3DAbstract Authors: Lindenbach BD Hepatitis C virus genome replication occurs in endoplasmic reticulum-derived membrane compartments, but it is unknown how these structures arise. In this issue of Cell Host & Microbe, Reiss and colleagues (2011) show that the virus recruits a specific lipid kinase to replication sites, stimulates its kinase activity, and alters the phospholipid profile of replication compartments. PMID: 21238940 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4399948 Thu, 20 Jan 2011 00:00:00 +0100 4399948 http://www.medworm.com/index.php?rid=4399947&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21238941%26dopt%3DAbstract Authors: Neil S Deletion of the nef gene from macaque simian immunodeficiency virus (SIVmac) attenuates its ability to cause disease. Pathogenic viruses occasionally emerge in macaques infected with Nef-deleted SIVmac, with some genetic determinants mapping to the envelope (env) gene. An intriguing new study shows that these changes endow Env with a Nef-like ability to counteract tetherin/BST2 (Serra-Moreno et al., 2011). PMID: 21238941 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4399947 Thu, 20 Jan 2011 00:00:00 +0100 4399947 http://www.medworm.com/index.php?rid=4399946&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21238942%26dopt%3DAbstract Authors: Abraham TM, Sarnow P Picornaviruses have evolved elaborate strategies to subvert host translation. In this issue of Cell Host and Microbe, Ho et al. (2011) report that enterovirus infection induces the synthesis of a transcription factor that enhances the synthesis of microRNA-141, which suppresses translation of the cap-binding protein, eIF4E, mRNA to inhibit cap-dependent translation. PMID: 21238942 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4399946 Thu, 20 Jan 2011 00:00:00 +0100 4399946 http://www.medworm.com/index.php?rid=4399945&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21238943%26dopt%3DAbstract Authors: Riglar DT, Richard D, Wilson DW, Boyle MJ, Dekiwadia C, Turnbull L, Angrisano F, Marapana DS, Rogers KL, Whitchurch CB, Beeson JG, Cowman AF, Ralph SA, Baum J Erythrocyte invasion by the merozoite is an obligatory stage in Plasmodium parasite infection and essential to malaria disease progression. Attempts to study this process have been hindered by the poor invasion synchrony of merozoites from the only in vitro culture-adapted human malaria parasite, Plasmodium falciparum. Using fluorescence, three-dimensional structured illumination, and immunoelectron microscopy of filtered merozoites, we analyze cellular and molecular events underlying each discrete step of invasion. Monitoring the dynamics of these events revealed that commitment to the process is mediated through meroz... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4399945 Thu, 20 Jan 2011 00:00:00 +0100 4399945 http://www.medworm.com/index.php?rid=4399944&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21238944%26dopt%3DAbstract Authors: Venugopal A, Bryk R, Shi S, Rhee K, Rath P, Schnappinger D, Ehrt S, Nathan C Mycobacterium tuberculosis (Mtb) adapts to persist in a nutritionally limited macrophage compartment. Lipoamide dehydrogenase (Lpd), the third enzyme (E3) in Mtb's pyruvate dehydrogenase complex (PDH), also serves as E1 of peroxynitrite reductase/peroxidase (PNR/P), which helps Mtb resist host-reactive nitrogen intermediates. In contrast to Mtb lacking dihydrolipoamide acyltransferase (DlaT), the E2 of PDH and PNR/P, Lpd-deficient Mtb is severely attenuated in wild-type and immunodeficient mice. This suggests that Lpd has a function that DlaT does not share. When DlaT is absent, Mtb upregulates an Lpd-dependent branched-chain keto acid dehydrogenase (BCKADH) encoded by pdhA, pdhB, pdhC, and lpdC. With... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4399944 Thu, 20 Jan 2011 00:00:00 +0100 4399944 http://www.medworm.com/index.php?rid=4399943&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21238945%26dopt%3DAbstract Authors: Reiss S, Rebhan I, Backes P, Romero-Brey I, Erfle H, Matula P, Kaderali L, Poenisch M, Blankenburg H, Hiet MS, Longerich T, Diehl S, Ramirez F, Balla T, Rohr K, Kaul A, Bühler S, Pepperkok R, Lengauer T, Albrecht M, Eils R, Schirmacher P, Lohmann V, Bartenschlager R Hepatitis C virus (HCV) is a major causative agent of chronic liver disease in humans. To gain insight into host factor requirements for HCV replication, we performed a siRNA screen of the human kinome and identified 13 different kinases, including phosphatidylinositol-4 kinase III alpha (PI4KIIIα), as being required for HCV replication. Consistent with elevated levels of the PI4KIIIα product phosphatidylinositol-4-phosphate (PI4P) detected in HCV-infected cultured hepatocytes and liver tissue from chronic hepat... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4399943 Thu, 20 Jan 2011 00:00:00 +0100 4399943 http://www.medworm.com/index.php?rid=4399942&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21238946%26dopt%3DAbstract Authors: Serra-Moreno R, Jia B, Breed M, Alvarez X, Evans DT Tetherin (BST-2 or CD317) is an interferon-inducible transmembrane protein that inhibits virus release from infected cells. Whereas HIV-1 Vpu and HIV-2 Env counteract human tetherin, most SIVs use Nef to antagonize the tetherin proteins of their nonhuman primate hosts. Here, we show that compensatory changes in the cytoplasmic domain of SIV gp41, acquired by a nef-deleted virus that regained a pathogenic phenotype in infected rhesus macaques, restore resistance to tetherin. These changes facilitate virus release in the presence of rhesus tetherin, but not human tetherin, and enhance virus replication in interferon-treated primary lymphocytes. The substitutions in gp41 result in a selective physical association with rhesus tet... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4399942 Thu, 20 Jan 2011 00:00:00 +0100 4399942 http://www.medworm.com/index.php?rid=4399941&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21238947%26dopt%3DAbstract Authors: Ho BC, Yu SL, Chen JJ, Chang SY, Yan BS, Hong QS, Singh S, Kao CL, Chen HY, Su KY, Li KC, Cheng CL, Cheng HW, Lee JY, Lee CN, Yang PC Viruses rely on the host translation machinery to complete their life cycles. Picornaviruses use an internal ribosome entry site to initiate cap-independent protein translation and in parallel host cap-dependent translation is shut off. This process is thought to occur primarily via cleavage of host translation initiation factors eIF4GI and eIF4GII by viral proteases. Here we describe another mechanism whereby miR-141 induced upon enterovirus infection targets the cap-dependent translation initiation factor, eIF4E, for shutoff of host protein synthesis. Knockdown of miR-141 reduces viral propagation, and silencing of eIF4E can completely reverse... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4399941 Thu, 20 Jan 2011 00:00:00 +0100 4399941 http://www.medworm.com/index.php?rid=4399940&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21238948%26dopt%3DAbstract Authors: Coyne CB, Bozym R, Morosky SA, Hanna SL, Mukherjee A, Tudor M, Kim KS, Cherry S Enteroviruses, including coxsackievirus B (CVB) and poliovirus (PV), can access the CNS through the blood brain barrier (BBB) endothelium to cause aseptic meningitis. To identify cellular components required for CVB and PV infection of human brain microvascular endothelial cells, an in vitro BBB model, we performed comparative RNAi screens and identified 117 genes that influenced infection. Whereas a large proportion of genes whose depletion enhanced infection (17 of 22) were broadly antienteroviral, only 46 of the 95 genes whose depletion inhibited infection were required by both CVB and PV and included components of cell signaling pathways such as adenylate cyclases. Downregulation of genes incl... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4399940 Thu, 20 Jan 2011 00:00:00 +0100 4399940 http://www.medworm.com/index.php?rid=4274308&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21147459%26dopt%3DAbstract Authors: Feng CG, Sher A To promote their survival, intracellular pathogens must confront microbicidal activities induced by interferons. In this issue of Cell Host & Microbe, Fentress et al. show that Toxoplasma gondii evades intracellular killing by deploying a virulence determinant, ROP18, which acts by directly phosphorylating and disabling an IFN-γ-inducible immunity-related GTPase involved in pathogen clearance. PMID: 21147459 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=4274308 Thu, 16 Dec 2010 00:00:00 +0100 4274308