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PLoS Pathogens

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https://www.readbyqxmd.com/read/28430827/dual-role-of-the-toxoplasma-gondii-clathrin-adaptor-ap1-in-the-sorting-of-rhoptry-and-microneme-proteins-and-in-parasite-division
#1
Kannan Venugopal, Elisabeth Werkmeister, Nicolas Barois, Jean-Michel Saliou, Anais Poncet, Ludovic Huot, Fabien Sindikubwabo, Mohamed Ali Hakimi, Gordon Langsley, Frank Lafont, Sabrina Marion
Toxoplasma gondii possesses a highly polarized secretory system, which efficiently assembles de novo micronemes and rhoptries during parasite replication. These apical secretory organelles release their contents into host cells promoting parasite invasion and survival. Using a CreLox-based inducible knock-out strategy and the ddFKBP over-expression system, we unraveled novel functions of the clathrin adaptor complex TgAP1. First, our data indicate that AP1 in T. gondii likely functions as a conserved heterotetrameric complex composed of the four subunits γ, β, μ1, σ1 and interacts with known regulators of clathrin-mediated vesicular budding such as the unique ENTH-domain containing protein, which we named Epsin-like protein (TgEpsL)...
April 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28430817/kaposi-sarcoma-herpesvirus-kshv-latency-associated-nuclear-antigen-lana-recruits-components-of-the-mrn-mre11-rad50-nbs1-repair-complex-to-modulate-an-innate-immune-signaling-pathway-and-viral-latency
#2
Giuseppe Mariggiò, Sandra Koch, Guigen Zhang, Magdalena Weidner-Glunde, Jessica Rückert, Semra Kati, Susann Santag, Thomas F Schulz
Kaposi Sarcoma Herpesvirus (KSHV), a γ2-herpesvirus and class 1 carcinogen, is responsible for at least three human malignancies: Kaposi Sarcoma (KS), Primary Effusion Lymphoma (PEL) and Multicentric Castleman's Disease (MCD). Its major nuclear latency protein, LANA, is indispensable for the maintenance and replication of latent viral DNA in infected cells. Although LANA is mainly a nuclear protein, cytoplasmic isoforms of LANA exist and can act as antagonists of the cytoplasmic DNA sensor, cGAS. Here, we show that cytosolic LANA also recruits members of the MRN (Mre11-Rad50-NBS1) repair complex in the cytosol and thereby inhibits their recently reported role in the sensing of cytoplasmic DNA and activation of the NF-κB pathway...
April 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426838/a-second-wave-of-salmonella-t3ss1-activity-prolongs-the-lifespan-of-infected-epithelial-cells
#3
Ciaran E Finn, Audrey Chong, Kendal G Cooper, Tregei Starr, Olivia Steele-Mortimer
Type III secretion system 1 (T3SS1) is used by the enteropathogen Salmonella enterica serovar Typhimurium to establish infection in the gut. Effector proteins translocated by this system across the plasma membrane facilitate invasion of intestinal epithelial cells. One such effector, the inositol phosphatase SopB, contributes to invasion and mediates activation of the pro-survival kinase Akt. Following internalization, some bacteria escape from the Salmonella-containing vacuole into the cytosol and there is evidence suggesting that T3SS1 is expressed in this subpopulation...
April 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426803/dendritic-cell-maturation-but-not-type-i-interferon-exposure-restricts-infection-by-htlv-1-and-viral-transmission-to-t-cells
#4
Gergès Rizkallah, Sandrine Alais, Nicolas Futsch, Yuetsu Tanaka, Chloé Journo, Renaud Mahieux, Hélène Dutartre
Human T lymphotropic Virus type 1 (HTLV-1) is the etiological agent of Adult T cell Leukemia/Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Both CD4+ T-cells and dendritic cells (DCs) infected with HTLV-1 are found in peripheral blood from HTLV-1 carriers. We previously demonstrated that monocyte-derived IL-4 DCs are more susceptible to HTLV-1 infection than autologous primary T-cells, suggesting that DC infection precedes T-cell infection. However, during blood transmission, breast-feeding or sexual transmission, HTLV-1 may encounter different DC subsets present in the blood, the intestinal or genital mucosa respectively...
April 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426751/the-role-of-microsporidian-polar-tube-protein-4-ptp4-in-host-cell-infection
#5
Bing Han, Valérie Polonais, Tatsuki Sugi, Rama Yakubu, Peter M Takvorian, Ann Cali, Keith Maier, Mengxian Long, Matthew Levy, Herbert B Tanowitz, Guoqing Pan, Frédéric Delbac, Zeyang Zhou, Louis M Weiss
Microsporidia have been identified as pathogens that have important effects on our health, food security and economy. A key to the success of these obligate intracellular pathogens is their unique invasion organelle, the polar tube, which delivers the nucleus containing sporoplasm into host cells during invasion. Due to the size of the polar tube, the rapidity of polar tube discharge and sporoplasm passage, and the absence of genetic techniques for the manipulation of microsporidia, study of this organelle has been difficult and there is relatively little known regarding polar tube formation and the function of the proteins making up this structure...
April 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28423062/filamentous-fungal-carbon-catabolite-repression-supports-metabolic-plasticity-and-stress-responses-essential-for-disease-progression
#6
Sarah R Beattie, Kenneth M K Mark, Arsa Thammahong, Laure Nicolas Annick Ries, Sourabh Dhingra, Alayna K Caffrey-Carr, Chao Cheng, Candice C Black, Paul Bowyer, Michael J Bromley, Joshua J Obar, Gustavo H Goldman, Robert A Cramer
Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. We propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. To this end, we find that A...
April 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28423057/insertion-of-a-ligand-to-her2-in-gb-retargets-hsv-tropism-and-obviates-the-need-for-activation-of-the-other-entry-glycoproteins
#7
Biljana Petrovic, Tatiana Gianni, Valentina Gatta, Gabriella Campadelli-Fiume
Herpes simplex virus (HSV) entry into the cells requires glycoproteins gD, gH/gL and gB, activated in a cascade fashion by conformational modifications induced by cognate receptors and intermolecular signaling. The receptors are nectin1 and HVEM (Herpes virus entry mediator) for gD, and αvβ6 or αvβ8 integrin for gH. In earlier work, insertion of a single chain antibody (scFv) to the cancer receptor HER2 (human epidermal growth factor receptor 2) in gD, or in gH, resulted in HSVs specifically retargeted to the HER2-positive cancer cells, hence in highly specific non-attenuated oncolytic agents...
April 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28419151/skin-resident-cd4-t-cells-protect-against-leishmania-major-by-recruiting-and-activating-inflammatory-monocytes
#8
Nelson D Glennie, Susan W Volk, Phillip Scott
Tissue-resident memory T cells are required for establishing protective immunity against a variety of different pathogens, although the mechanisms mediating protection by CD4+ resident memory T cells are still being defined. In this study we addressed this issue with a population of protective skin-resident, IFNγ-producing CD4+ memory T cells generated following Leishmania major infection. We previously found that resident memory T cells recruit circulating effector T cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate the delayed-hypersensitivity response observed in immune mice and provide protection without circulating T cells...
April 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28414785/the-epstein-barr-virus-mir-bhrf1-1-targets-rnf4-during-productive-infection-to-promote-the-accumulation-of-sumo-conjugates-and-the-release-of-infectious-virus
#9
Jinlin Li, Simone Callegari, Maria G Masucci
Post-translational modification by the Small Ubiquitin-like Modifier (SUMO) regulates a variety of cellular functions, and is hijacked by viruses to remodel the host cell during latent and productive infection. Here we have monitored the activity of the SUMO conjugation machinery in cells productively infected with Epstein-Barr virus (EBV). We found that SUMO2/3 conjugates accumulate during the late phase of the productive virus cycle, and identified several viral proteins as bone fide SUMOylation substrates...
April 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28414774/mycobacterium-marinum-antagonistically-induces-an-autophagic-response-while-repressing-the-autophagic-flux-in-a-torc1-and-esx-1-dependent-manner
#10
Elena Cardenal-Muñoz, Sonia Arafah, Ana Teresa López-Jiménez, Sébastien Kicka, Alexandra Falaise, Frauke Bach, Olivier Schaad, Jason S King, Monica Hagedorn, Thierry Soldati
Autophagy is a eukaryotic catabolic process also participating in cell-autonomous defence. Infected host cells generate double-membrane autophagosomes that mature in autolysosomes to engulf, kill and digest cytoplasmic pathogens. However, several bacteria subvert autophagy and benefit from its machinery and functions. Monitoring infection stages by genetics, pharmacology and microscopy, we demonstrate that the ESX-1 secretion system of Mycobacterium marinum, a close relative to M. tuberculosis, upregulates the transcription of autophagy genes, and stimulates autophagosome formation and recruitment to the mycobacteria-containing vacuole (MCV) in the host model organism Dictyostelium...
April 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28414768/gpatch3-negatively-regulates-rlr-mediated-innate-antiviral-responses-by-disrupting-the-assembly-of-visa-signalosome
#11
Ying Nie, Yong Ran, Hong-Yan Zhang, Zhe-Fu Huang, Zhao-Yi Pan, Su-Yun Wang, Yan-Yi Wang
Upon viral infection, retinoic acid-inducible gene I-like receptors (RLRs) recognize viral RNA and trigger a series of signaling events, leading to the induction of type I interferons (IFNs). These processes are delicately regulated to prevent excessive and harmful immune responses. In this study, we identified G patch domain-containing protein 3 (GPATCH3) as a negative regulator of RLR-mediated antiviral signaling pathways. Overexpression of GPATCH3 impaired RNA virus- triggered induction of downstream antiviral genes, whereas its knockdown had opposite effects and attenuated viral replication...
April 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28410427/tcr-stimulation-strength-is-inversely-associated-with-establishment-of-functional-brain-resident-memory-cd8-t-cells-during-persistent-viral-infection
#12
Saumya Maru, Ge Jin, Todd D Schell, Aron E Lukacher
Establishing functional tissue-resident memory (TRM) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells...
April 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28410407/bacterial-amyloid-curli-acts-as-a-carrier-for-dna-to-elicit-an-autoimmune-response-via-tlr2-and-tlr9
#13
Sarah A Tursi, Ernest Y Lee, Nicole J Medeiros, Michael H Lee, Lauren K Nicastro, Bettina Buttaro, Stefania Gallucci, Ronald Paul Wilson, Gerard C L Wong, Çagla Tükel
Bacterial biofilms are associated with numerous human infections. The predominant protein expressed in enteric biofilms is the amyloid curli, which forms highly immunogenic complexes with DNA. Infection with curli-expressing bacteria or systemic exposure to purified curli-DNA complexes triggers autoimmunity via the generation of type I interferons (IFNs) and anti-double-stranded DNA antibodies. Here, we show that DNA complexed with amyloid curli powerfully stimulates Toll-like receptor 9 (TLR9) through a two-step mechanism...
April 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28410401/ripk3-interacts-with-mavs-to-regulate-type-i-ifn-mediated-immunity-to-influenza-a-virus-infection
#14
Jeffrey Downey, Erwan Pernet, François Coulombe, Benoit Allard, Isabelle Meunier, Joanna Jaworska, Salman Qureshi, Donald C Vinh, James G Martin, Philippe Joubert, Maziar Divangahi
The type I interferon pathway plays a critical role in both host defense and tolerance against viral infection and thus requires refined regulatory mechanisms. RIPK3-mediated necroptosis has been shown to be involved in anti-viral immunity. However, the exact role of RIPK3 in immunity to Influenza A Virus (IAV) is poorly understood. In line with others, we, herein, show that Ripk3-/- mice are highly susceptible to IAV infection, exhibiting elevated pulmonary viral load and heightened morbidity and mortality...
April 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28384349/neutrophils-and-ly6chi-monocytes-collaborate-in-generating-an-optimal-cytokine-response-that-protects-against-pulmonary-legionella-pneumophila-infection
#15
Cierra N Casson, Jessica L Doerner, Alan M Copenhaver, Jasmine Ramirez, Alicia M Holmgren, Mark A Boyer, Ingharan J Siddarthan, Sara H Rouhanifard, Arjun Raj, Sunny Shin
Early responses mounted by both tissue-resident and recruited innate immune cells are essential for host defense against bacterial pathogens. In particular, both neutrophils and Ly6Chi monocytes are rapidly recruited to sites of infection. While neutrophils and monocytes produce bactericidal molecules, such as reactive nitrogen and oxygen species, both cell types are also capable of synthesizing overlapping sets of cytokines important for host defense. Whether neutrophils and monocytes perform redundant or non-redundant functions in the generation of anti-microbial cytokine responses remains elusive...
April 6, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426825/levels-of-hiv-1-persistence-on-antiretroviral-therapy-are-not-associated-with-markers-of-inflammation-or-activation
#16
Rajesh T Gandhi, Deborah K McMahon, Ronald J Bosch, Christina M Lalama, Joshua C Cyktor, Bernard J Macatangay, Charles R Rinaldo, Sharon A Riddler, Evelyn Hogg, Catherine Godfrey, Ann C Collier, Joseph J Eron, John W Mellors
Antiretroviral therapy (ART) reduces levels of HIV-1 and immune activation but both can persist despite clinically effective ART. The relationships among pre-ART and on-ART levels of HIV-1 and activation are incompletely understood, in part because prior studies have been small or cross-sectional. To address these limitations, we evaluated measures of HIV-1 persistence, inflammation, T cell activation and T cell cycling in a longitudinal cohort of 101 participants who initiated ART and had well-documented sustained suppression of plasma viremia for a median of 7 years...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426821/the-importance-of-model-systems-why-we-study-a-virus-on-the-brink-of-global-eradication
#17
Julie K Pfeiffer
No abstract text is available yet for this article.
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426789/gre-factors-mediated-control-of-hild-transcription-is-essential-for-the-invasion-of-epithelial-cells-by-salmonella-enterica-serovar-typhimurium
#18
Tania Gaviria-Cantin, Youssef El Mouali, Soazig Le Guyon, Ute Römling, Carlos Balsalobre
The invasion of epithelial cells by Salmonella enterica serovar Typhimurium is a very tightly regulated process. Signaling cascades triggered by different environmental and physiological signals converge to control HilD, an AraC regulator that coordinates the expression of several virulence factors. The expression of hilD is modulated at several steps of the expression process. Here, we report that the invasion of epithelial cells by S. Typhimurium strains lacking the Gre factors, GreA and GreB, is impaired...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426777/rotavirus-genome-replication-some-assembly-required
#19
Courtney P Long, Sarah M McDonald
No abstract text is available yet for this article.
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426766/activated-entomopathogenic-nematode-infective-juveniles-release-lethal-venom-proteins
#20
Dihong Lu, Marissa Macchietto, Dennis Chang, Mirayana M Barros, James Baldwin, Ali Mortazavi, Adler R Dillman
Entomopathogenic nematodes (EPNs) are unique parasites due to their symbiosis with entomopathogenic bacteria and their ability to kill insect hosts quickly after infection. It is widely believed that EPNs rely on their bacterial partners for killing hosts. Here we disproved this theory by demonstrating that the in vitro activated infective juveniles (IJs) of Steinernema carpocapsae (a well-studied EPN species) release venom proteins that are lethal to several insects including Drosophila melanogaster. We confirmed that the in vitro activation is a good approximation of the in vivo process by comparing the transcriptomes of individual in vitro and in vivo activated IJs...
April 2017: PLoS Pathogens
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