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PLoS Pathogens

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https://www.readbyqxmd.com/read/27930733/phosphorylation-of-eukaryotic-initiation-factor-2%C3%AE-during-stress-and-encystation-in-entamoeba-species
#1
Holland M Hendrick, Brenda H Welter, Matthew A Hapstack, Steven E Sykes, William J Sullivan, Lesly A Temesvari
Entamoeba histolytica is an enteric pathogen responsible for amoebic dysentery and liver abscess. It alternates between the host-restricted trophozoite form and the infective environmentally-stable cyst stage. Throughout its lifecycle E. histolytica experiences stress, in part, from host immune pressure. Conversion to cysts is presumed to be a stress-response. In other systems, stress induces phosphorylation of a serine residue on eukaryotic translation initiation factor-2α (eIF2α). This inhibits eIF2α activity resulting in a general decline in protein synthesis...
December 8, 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27923068/gene-expression-correlates-with-the-number-of-herpes-viral-genomes-initiating-infection-in-single-cells
#2
Efrat M Cohen, Oren Kobiler
Viral gene expression varies significantly among genetically identical cells. The sources of these variations are not well understood and have been suggested to involve both deterministic host differences and stochastic viral host interactions. For herpesviruses, only a limited number of incoming viral genomes initiate expression and replication in each infected cell. To elucidate the effect of this limited number of productively infecting genomes on viral gene expression in single cells, we constructed a set of fluorescence-expressing genetically tagged herpes recombinants...
December 6, 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27930749/exploitation-of-the-host-cell-membrane-fusion-machinery-by-leishmania-is-part-of-the-infection-process
#3
Christine Matte, Albert Descoteaux
No abstract text is available yet for this article.
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27930745/the-ebola-interferon-inhibiting-domains-attenuate-and-dysregulate-cell-mediated-immune-responses
#4
Ndongala Michel Lubaki, Patrick Younan, Rodrigo I Santos, Michelle Meyer, Mathieu Iampietro, Richard A Koup, Alexander Bukreyev
Ebola virus (EBOV) infections are characterized by deficient T-lymphocyte responses, T-lymphocyte apoptosis and lymphopenia. We previously showed that disabling of interferon-inhibiting domains (IIDs) in the VP24 and VP35 proteins effectively unblocks maturation of dendritic cells (DCs) and increases the secretion of cytokines and chemokines. Here, we investigated the role of IIDs in adaptive and innate cell-mediated responses using recombinant viruses carrying point mutations, which disabled IIDs in VP24 (EBOV/VP24m), VP35 (EBOV/VP35m) or both (EBOV/VP35m/VP24m)...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27930735/gene-editing-approaches-against-viral-infections-and-strategy-to-prevent-occurrence-of-viral-escape
#5
Martyn K White, Wenhui Hu, Kamel Khalili
No abstract text is available yet for this article.
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926947/correction-cd40-activation-rescues-antiviral-cd8-t-cells-from-pd-1-mediated-exhaustion
#6
Masanori Isogawa, Josan Chung, Yasuhiro Murata, Kazuhiro Kakimi, Francis V Chisari
[This corrects the article DOI: 10.1371/journal.ppat.1003490.].
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926944/targeting-neutrophils-to-prevent-malaria-associated-acute-lung-injury-acute-respiratory-distress-syndrome-in-mice
#7
Michelle K Sercundes, Luana S Ortolan, Daniela Debone, Paulo V Soeiro-Pereira, Eliane Gomes, Elizabeth H Aitken, Antonio Condino Neto, Momtchilo Russo, Maria R D' Império Lima, José M Alvarez, Silvia Portugal, Claudio R F Marinho, Sabrina Epiphanio
Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. When manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We have previously shown that a proportion of DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. Herein, we investigated the role of neutrophils in the pathogenesis of malaria-associated ALI/ARDS...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926943/the-mouse-cytomegalovirus-gene-m42-targets-surface-expression-of-the-protein-tyrosine-phosphatase-cd45-in-infected-macrophages
#8
Nadine Thiel, Kirsten A Keyser, Niels A W Lemmermann, Jennifer D Oduro, Karen Wagner, Carina Elsner, Anne Halenius, Tihana Lenac Roviš, Melanie M Brinkmann, Stipan Jonjić, Luka Cicin-Sain, Martin Messerle
The receptor-like protein tyrosine phosphatase CD45 is expressed on the surface of cells of hematopoietic origin and has a pivotal role for the function of these cells in the immune response. Here we report that following infection of macrophages with mouse cytomegalovirus (MCMV) the cell surface expression of CD45 is drastically diminished. Screening of a set of MCMV deletion mutants allowed us to identify the viral gene m42 of being responsible for CD45 down-modulation. Moreover, expression of m42 independent of viral infection upon retroviral transduction of the RAW264...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926942/actin-related-protein-2-arp2-and-virus-induced-filopodia-facilitate-human-respiratory-syncytial-virus-spread
#9
Masfique Mehedi, Thomas McCarty, Scott E Martin, Cyril Le Nouën, Eugen Buehler, Yu-Chi Chen, Margery Smelkinson, Sundar Ganesan, Elizabeth R Fischer, Linda G Brock, Bo Liang, Shirin Munir, Peter L Collins, Ursula J Buchholz
Human respiratory syncytial virus (RSV) is an enveloped RNA virus that is the most important viral cause of acute pediatric lower respiratory tract illness worldwide, and lacks a vaccine or effective antiviral drug. The involvement of host factors in the RSV replicative cycle remains poorly characterized. A genome-wide siRNA screen in human lung epithelial A549 cells identified actin-related protein 2 (ARP2) as a host factor involved in RSV infection. ARP2 knockdown did not reduce RSV entry, and did not markedly reduce gene expression during the first 24 hr of infection, but decreased viral gene expression thereafter, an effect that appeared to be due to inhibition of viral spread to neighboring cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926941/type-1-interferons-and-nk-cells-limit-murine-cytomegalovirus-escape-from-the-lymph-node-subcapsular-sinus
#10
Helen E Farrell, Kimberley Bruce, Clara Lawler, Rhonda D Cardin, Nicholas J Davis-Poynter, Philip G Stevenson
Cytomegaloviruses (CMVs) establish chronic, systemic infections. Peripheral infection spreads via lymph nodes, which are also a focus of host defence. Thus, this is a point at which systemic infection spread might be restricted. Subcapsular sinus macrophages (SSM) captured murine CMV (MCMV) from the afferent lymph and poorly supported its replication. Blocking the type I interferon (IFN-I) receptor (IFNAR) increased MCMV infection of SSM and of the fibroblastic reticular cells (FRC) lining the subcapsular sinus, and accelerated viral spread to the spleen...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926940/inflammasome-independent-nlrp3-restriction-of-a-protective-early-neutrophil-response-to-pulmonary-tularemia
#11
Sivakumar Periasamy, Hongnga T Le, Ellen B Duffy, Heather Chin, Jonathan A Harton
Francisella tularensis (Ft) causes a frequently fatal, acute necrotic pneumonia in humans and animals. Following lethal Ft infection in mice, infiltration of the lungs by predominantly immature myeloid cells and subsequent myeloid cell death drive pathogenesis and host mortality. However, following sub-lethal Ft challenge, more mature myeloid cells are elicited and are protective. In addition, inflammasome-dependent IL-1β and IL-18 are important for protection. As Nlrp3 appears dispensable for resistance to infection with Francisella novicida, we considered its role during infection with the virulent Type A strain SchuS4 and the attenuated Type B live vaccine strain LVS...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926931/microbial-translocation-and-inflammation-occur-in-hyperacute-immunodeficiency-virus-infection-and-compromise-host-control-of-virus-replication
#12
Adam J Ericsen, Michael Lauck, Mariel S Mohns, Sarah R DiNapoli, James P Mutschler, Justin M Greene, Jason T Weinfurter, Gabrielle Lehrer-Brey, Trent M Prall, Samantha M Gieger, Connor R Buechler, Kristin A Crosno, Eric J Peterson, Matthew R Reynolds, Roger W Wiseman, Benjamin J Burwitz, Jacob D Estes, Jonah B Sacha, Thomas C Friedrich, Jason M Brenchley, David H O'Connor
Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926930/cytomegalovirus-specific-il-10-producing-cd4-t-cells-are-governed-by-type-i-ifn-induced-il-27-and-promote-virus-persistence
#13
Mathew Clement, Morgan Marsden, Maria A Stacey, Juneid Abdul-Karim, Silvia Gimeno Brias, Diana Costa Bento, Martin J Scurr, Peter Ghazal, Casey T Weaver, Gianluca Carlesso, Simon Clare, Simon A Jones, Andrew Godkin, Gareth W Jones, Ian R Humphreys
CD4+ T cells support host defence against herpesviruses and other viral pathogens. We identified that CD4+ T cells from systemic and mucosal tissues of hosts infected with the β-herpesviridae human cytomegalovirus (HCMV) or murine cytomegalovirus (MCMV) express the regulatory cytokine interleukin (IL)-10. IL-10+CD4+ T cells co-expressed TH1-associated transcription factors and chemokine receptors. Mice lacking T cell-derived IL-10 elicited enhanced antiviral T cell responses and restricted MCMV persistence in salivary glands and secretion in saliva...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926929/functional-and-evolutionary-analyses-identify-proteolysis-as-a-general-mechanism-for-nlrp1-inflammasome-activation
#14
Joseph Chavarría-Smith, Patrick S Mitchell, Alvin M Ho, Matthew D Daugherty, Russell E Vance
Inflammasomes are cytosolic multi-protein complexes that initiate immune responses to infection by recruiting and activating the Caspase-1 protease. Human NLRP1 was the first protein shown to form an inflammasome, but its physiological mechanism of activation remains unknown. Recently, specific variants of mouse and rat NLRP1 were found to be activated upon N-terminal cleavage by the anthrax lethal factor protease. However, agonists for other NLRP1 variants, including human NLRP1, are not known, and it remains unclear if they are also activated by proteolysis...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926928/an-interactome-centered-protein-discovery-approach-reveals-novel-components-involved-in-mitosome-function-and-homeostasis-in-giardia-lamblia
#15
Samuel Rout, Jon Paulin Zumthor, Elisabeth M Schraner, Carmen Faso, Adrian B Hehl
Protozoan parasites of the genus Giardia are highly prevalent globally, and infect a wide range of vertebrate hosts including humans, with proliferation and pathology restricted to the small intestine. This narrow ecological specialization entailed extensive structural and functional adaptations during host-parasite co-evolution. An example is the streamlined mitosomal proteome with iron-sulphur protein maturation as the only biochemical pathway clearly associated with this organelle. Here, we applied techniques in microscopy and protein biochemistry to investigate the mitosomal membrane proteome in association to mitosome homeostasis...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27923071/c-type-lectin-mincle-recognizes-glucosyl-diacylglycerol-of-streptococcus-pneumoniae-and-plays-a-protective-role-in-pneumococcal-pneumonia
#16
Friederike Behler-Janbeck, Tomotsugu Takano, Regina Maus, Jennifer Stolper, Danny Jonigk, Meritxell Tort Tarrés, Thomas Fuehner, Antje Prasse, Tobias Welte, Mattie S M Timmer, Bridget L Stocker, Yoichi Nakanishi, Tomofumi Miyamoto, Sho Yamasaki, Ulrich A Maus
Among various innate immune receptor families, the role of C-type lectin receptors (CLRs) in lung protective immunity against Streptococcus pneumoniae (S. pneumoniae) is not fully defined. We here show that Mincle gene expression was induced in alveolar macrophages and neutrophils in bronchoalveolar lavage fluids of mice and patients with pneumococcal pneumonia. Moreover, S. pneumoniae directly triggered Mincle reporter cell activation in vitro via its glycolipid glucosyl-diacylglycerol (Glc-DAG), which was identified as the ligand recognized by Mincle...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27923070/macrophage-colony-stimulating-factor-derived-from-cd4-t-cells-contributes-to-control-of-a-blood-borne-infection
#17
Mary F Fontana, Gabrielly L de Melo, Chioma Anidi, Rebecca Hamburger, Chris Y Kim, So Youn Lee, Jennifer Pham, Charles C Kim
Dynamic regulation of leukocyte population size and activation state is crucial for an effective immune response. In malaria, Plasmodium parasites elicit robust host expansion of macrophages and monocytes, but the underlying mechanisms remain unclear. Here we show that myeloid expansion during P. chabaudi infection is dependent upon both CD4+ T cells and the cytokine Macrophage Colony Stimulating Factor (MCSF). Single-cell RNA-Seq analysis on antigen-experienced T cells revealed robust expression of Csf1, the gene encoding MCSF, in a sub-population of CD4+ T cells with distinct transcriptional and surface phenotypes...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27923069/characterization-in-helicobacter-pylori-of-a-nickel-transporter-essential-for-colonization-that-was-acquired-during-evolution-by-gastric-helicobacter-species
#18
Frédéric Fischer, Marie Robbe-Saule, Evelyne Turlin, Francesco Mancuso, Valérie Michel, Pierre Richaud, Frédéric J Veyrier, Hilde De Reuse, Daniel Vinella
Metal acquisition is crucial for all cells and for the virulence of many bacterial pathogens. In particular, nickel is a virulence determinant for the human gastric pathogen Helicobacter pylori as it is the cofactor of two enzymes essential for in vivo colonization, urease and a [NiFe] hydrogenase. To import nickel despite its scarcity in the human body, H. pylori requires efficient uptake mechanisms that are only partially defined. Indeed, alternative ways of nickel entry were predicted to exist in addition to the well-described NixA permease...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27918748/the-cxcl12-cxcr4-signaling-pathway-a-new-susceptibility-factor-in-human-papillomavirus-pathogenesis
#19
Floriane Meuris, Laetitia Carthagena, Agnieszka Jaracz-Ros, Françoise Gaudin, Pasquale Cutolo, Claire Deback, Yuezhen Xue, Françoise Thierry, John Doorbar, Françoise Bachelerie
The productive human papillomavirus (HPV) life cycle is tightly linked to the differentiation and cycling of keratinocytes. Deregulation of these processes and stimulation of cell proliferation by the action of viral oncoproteins and host cell factors underlies HPV-mediated carcinogenesis. Severe HPV infections characterize the wart, hypogammaglobulinemia, infection, and myelokathexis (WHIM) immunodeficiency syndrome, which is caused by gain-of-function mutations in the CXCR4 receptor for the CXCL12 chemokine, one of which is CXCR41013...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27911947/the-yersinia-pestis-effector-yopm-inhibits-pyrin-inflammasome-activation
#20
Dmitry Ratner, M Pontus A Orning, Megan K Proulx, Donghai Wang, Mikhail A Gavrilin, Mark D Wewers, Emad S Alnemri, Peter F Johnson, Bettina Lee, Joan Mecsas, Nobuhiko Kayagaki, Jon D Goguen, Egil Lien
Type III secretion systems (T3SS) are central virulence factors for many pathogenic Gram-negative bacteria, and secreted T3SS effectors can block key aspects of host cell signaling. To counter this, innate immune responses can also sense some T3SS components to initiate anti-bacterial mechanisms. The Yersinia pestis T3SS is particularly effective and sophisticated in manipulating the production of pro-inflammatory cytokines IL-1β and IL-18, which are typically processed into their mature forms by active caspase-1 following inflammasome formation...
December 2016: PLoS Pathogens
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