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Journal PLoS Pathog.

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HIV-1 variants are archived throughout infection and persist in the reservoir.

Kelsie Brooks, Bradley R Jones, Dario A Dilernia, Daniel J Wilkins, Daniel T Claiborne, Samantha McInally, Jill Gilmour, William Kilembe, Jeffrey B Joy, Susan A Allen, Zabrina L Brumme, Eric Hunter,

The HIV-1 reservoir consists of latently infected cells that persist despite antiretroviral therapy (ART). Elucidating the proviral genetic composition of the reservoir, particularly in the context of pre-therapy viral diversity, is therefore important to understanding reservoir formation and the persistence of latently infected cells. Here we investigate reservoir proviral variants ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(6):e1008378]

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Tn-Seq reveals hidden complexity in the utilization of host-derived glutathione in Francisella tularensis.

Kathryn M Ramsey, Hannah E Ledvina, Tenayaann M Tresko, Jamie M Wandzilak, Catherine A Tower, Thomas Tallo, Caroline E Schramm, S Brook Peterson, Shawn J Skerrett, Joseph D Mougous, Simon L Dove,

Host-derived glutathione (GSH) is an essential source of cysteine for the intracellular pathogen Francisella tularensis. In a comprehensive transposon insertion sequencing screen, we identified several F. tularensis genes that play central and previously unappreciated roles in the utilization of GSH during the growth of the bacterium in macrophages. We show ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(6):e1008566]

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A de novo approach to inferring within-host fitness effects during untreated HIV-1 infection.

Christopher J R Illingworth, Jayna Raghwani, David Serwadda, Nelson K Sewankambo, Merlin L Robb, Michael A Eller, Andrew R Redd, Thomas C Quinn, Katrina A Lythgoe,

In the absence of effective antiviral therapy, HIV-1 evolves in response to the within-host environment, of which the immune system is an important aspect. During the earliest stages of infection, this process of evolution is very rapid, driven by a small number of CTL escape mutations. As the infection progresses, ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(6):e1008171]

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Cellular plasticity of pathogenic fungi during infection.

Kenya E Fernandes, Dee A Carter,

PLoS Pathog. (PLoS pathogens)
[2020, 16(6):e1008571]

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Microbiome factors in HPV-driven carcinogenesis and cancers.

Daniel Lin, Ramez Kouzy, Joseph Abi Jaoude, Sonal S Noticewala, Andrea Y Delgado Medrano, Ann H Klopp, Cullen M Taniguchi, Lauren E Colbert,

PLoS Pathog. (PLoS pathogens)
[2020, 16(6):e1008524]

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Translational profiling of macrophages infected with Leishmania donovani identifies mTOR- and eIF4A-sensitive immune-related transcripts.

Visnu Chaparro, Louis-Philippe Leroux, Laia Masvidal, Julie Lorent, Tyson E Graber, Aude Zimmermann, Guillermo Arango Duque, Albert Descoteaux, Tommy Alain, Ola Larsson, Maritza Jaramillo,

The protozoan parasite Leishmania donovani (L. donovani) causes visceral leishmaniasis, a chronic infection which is fatal when untreated. Herein, we investigated whether in addition to altering transcription, L. donovani modulates host mRNA translation to establish a successful infection. Polysome-profiling revealed that one third of protein-coding mRNAs expressed in primary mouse ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(6):e1008291]

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In silico veritas? Potential limitations for SARS-CoV-2 vaccine development based on T-cell epitope prediction.

Sandra Silva-Arrieta, Philip J R Goulder, Christian Brander,

PLoS Pathog. (PLoS pathogens)
[2020, 16(6):e1008607]

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Different roles of integrin-β1 and integrin-αv for type IV secretion of CagA versus cell elongation phenotype and cell lifting by Helicobacter pylori.

Wolfgang Fischer, Rainer Haas,

PLoS Pathog. (PLoS pathogens)
[2020, 16(6):e1008564]

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Exploring potential of vaginal Lactobacillus isolates from South African women for enhancing treatment for bacterial vaginosis.

Anna-Ursula Happel, Brian Kullin, Hoyam Gamieldien, Nicole Wentzel, Chambrez Z Zauchenberger, Heather B Jaspan, Smritee Dabee, Shaun L Barnabas, Shameem Z Jaumdally, Janan Dietrich, Glenda Gray, Linda-Gail Bekker, Remy Froissart, Jo-Ann S Passmore,

Antibiotics continue to be the standard-of-care for bacterial vaginosis (BV), although recurrence rates are high. Vaginal probiotics may improve durability of BV treatment, although few probiotics for vaginal health contain Lactobacillus spp. that commonly colonize the lower female genital tract. Characteristics of vaginal Lactobacillus strains from South African women were ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(6):e1008559]

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Potent, specific MEPicides for treatment of zoonotic staphylococci.

Rachel L Edwards, Isabel Heueck, Soon Goo Lee, Ishaan T Shah, Justin J Miller, Andrew J Jezewski, Marwa O Mikati, Xu Wang, Robert C Brothers, Kenneth M Heidel, Damon M Osbourn, Carey-Ann D Burnham, Sophie Alvarez, Stephanie A Fritz, Cynthia S Dowd, Joseph M Jez, Audrey R Odom John,

Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact zoonoses that cause serious infections ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(6):e1007806]

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ATM-mediated DNA double-strand break response facilitated oncolytic Newcastle disease virus replication and promoted syncytium formation in tumor cells.

Shanhui Ren, Zaib Ur Rehman, Bo Gao, Zengqi Yang, Jiyong Zhou, Chunchun Meng, Cuiping Song, Venugopal Nair, Yingjie Sun, Chan Ding,

Deoxyribonucleic acid (DNA) damage response (DDR) is the fundamental cellular response for maintaining genomic integrity and suppressing tumorigenesis. The activation of ataxia telangiectasia-mutated (ATM) kinase is central to DNA double-strand break (DSB) for maintaining host-genome integrity in mammalian cells. Oncolytic Newcastle disease virus (NDV) can selectively replicate in tumor cells; ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(6):e1008514]

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Effector specificity and function in Drosophila innate immunity: Getting AMPed and dropping Boms.

Samuel J H Lin, Lianne B Cohen, Steven A Wasserman,

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008480]

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Zygote morphogenesis but not the establishment of cell polarity in Plasmodium berghei is controlled by the small GTPase, RAB11A.

Harshal Patil, Katie R Hughes, Leandro Lemgruber, Nisha Philip, Nicholas Dickens, G Lucas Starnes, Andrew P Waters,

Plasmodium species are apicomplexan parasites whose zoites are polarized cells with a marked apical organisation where the organelles associated with host cell invasion and colonization reside. Plasmodium gametes mate in the mosquito midgut to form the spherical and presumed apolar zygote that morphs during the following 24 hours into a ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008091]

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Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages.

Yong Cheng, Nicholas J Kiene, Alexandra Tatarian, Emily F Eix, Jeffrey S Schorey,

Mycobacterial infection leads to activation of the RIG-I/MAVS/TBK1 RNA sensing pathway in macrophages but the consequences of this activation remains poorly defined. In this study, we determined that activation of this RNA sensing pathway stimulates ICAM-1 expression in M.avium-infected macrophage through the inhibition of the E3 ubiquitin ligase CRL4COP1/DET1. CRL4 ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008569]

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Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication.

Kannan Venugopal, Sylia Chehade, Elisabeth Werkmeister, Nicolas Barois, Javier Periz, Frank Lafont, Isabelle Tardieux, Jamal Khalife, Gordon Langsley, Markus Meissner, Sabrina Marion,

Toxoplasma gondii possesses an armada of secreted virulent factors that enable parasite invasion and survival into host cells. These factors are contained in specific secretory organelles, the rhoptries, micronemes and dense granules that release their content upon host cell recognition. Dense granules are secreted in a constitutive manner during parasite ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008106]

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Mitochondrial reactive oxygen species as major effectors of antimicrobial immunity.

Elena Shekhova,

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008470]

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Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.

Gregory A Taylor, Hsin-I Huang, Brian E Fee, Nourhan Youssef, Mark L Jewell, Viviana Cantillana, Alexi A Schoenborn, Allison R Rogala, Anne F Buckley, Carl G Feng, Bruce A Vallance, Ajay S Gulati, Gianna E Hammer,

IRGM and its mouse orthologue Irgm1 are dynamin-like proteins that regulate vesicular remodeling, intracellular microbial killing, and pathogen immunity. IRGM dysfunction is linked to inflammatory bowel disease (IBD), and while it is thought that defective intracellular killing of microbes underscores IBD susceptibility, studies have yet to address how IRGM/Irgm1 regulates ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008553]

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Host syndecan-1 promotes listeriosis by inhibiting intravascular neutrophil extracellular traps.

Rafael S Aquino, Atsuko Hayashida, Pyong Woo Park,

Heparan sulfate proteoglycans (HSPGs) are at the forefront of host-microbe interactions. Molecular and cell-based studies suggest that HSPG-pathogen interactions promote pathogenesis by facilitating microbial attachment and invasion of host cells. However, the specific identity of HSPGs, precise mechanisms by which HSPGs promote pathogenesis, and the in vivo relevance of HSPG-pathogen ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008497]

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A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity.

Roberta M O'Connor, Felix J Nepveux V, Jaypee Abenoja, Gregory Bowden, Patricia Reis, Josiah Beaushaw, Rachel M Bone Relat, Iwona Driskell, Fernanda Gimenez, Michael W Riggs, Deborah A Schaefer, Eric W Schmidt, Zhenjian Lin, Daniel L Distel, Jon Clardy, Timothy R Ramadhar, David R Allred, Heather M Fritz, Pradipsinh Rathod, Laura Chery, John White,

Apicomplexan parasites cause severe disease in both humans and their domesticated animals. Since these parasites readily develop drug resistance, development of new, effective drugs to treat infection caused by these parasites is an ongoing challenge for the medical and veterinary communities. We hypothesized that invertebrate-bacterial symbioses might be a rich ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008600]

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Experimental determination of the force of malaria infection reveals a non-linear relationship to mosquito sporozoite loads.

Maya Aleshnick, Vitaly V Ganusov, Gibran Nasir, Gayane Yenokyan, Photini Sinnis,

Plasmodium sporozoites are the infective stage of the malaria parasite. Though this is a bottleneck for the parasite, the quantitative dynamics of transmission, from mosquito inoculation of sporozoites to patent blood-stage infection in the mammalian host, are poorly understood. Here we utilize a rodent model to determine the probability of ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008181]

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Toxoplasma  GRA15 and GRA24 are important activators of the host innate immune response in the absence of TLR11.

Debanjan Mukhopadhyay, David Arranz-Solís, Jeroen P J Saeij,

The murine innate immune response against Toxoplasma gondii is predominated by the interaction of TLR11/12 with Toxoplasma profilin. However, mice lacking Tlr11 or humans, who do not have functional TLR11 or TLR12, still elicit a strong innate immune response upon Toxoplasma infection. The parasite factors that determine this immune response ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008586]

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Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival.

Michael D Schultz, Tulin Dadali, Sylvain A Jacques, Hélène Muller-Steffner, Jeremy B Foote, Leonardo Sorci, Esther Kellenberger, Davide Botta, Frances E Lund,

NAD, a key co-enzyme required for cell metabolism, is synthesized via two pathways in most organisms. Since schistosomes apparently lack enzymes required for de novo NAD biosynthesis, we evaluated whether these parasites, which infect >200 million people worldwide, maintain NAD homeostasis via the NAD salvage biosynthetic pathway. We found that ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008539]

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Bactericidal type IV secretion system homeostasis in Xanthomonas citri.

William Cenens, Maxuel O Andrade, Edgar Llontop, Cristina E Alvarez-Martinez, Germán G Sgro, Chuck S Farah,

Several Xanthomonas species have a type IV secretion system (T4SS) that injects a cocktail of antibacterial proteins into neighbouring Gram-negative bacteria, often leading to rapid lysis upon cell contact. This capability represents an obvious fitness benefit since it can eliminate competition while the liberated contents of the lysed bacteria could ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008561]

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Antibody-induced internalisation of retroviral envelope glycoproteins is a signal initiation event.

Veera Panova, Jan Attig, George R Young, Jonathan P Stoye, George Kassiotis,

As obligate parasites, viruses highjack, modify and repurpose the cellular machinery for their own replication. Viral proteins have, therefore, evolved biological functions, such as signalling potential, that alter host cell physiology in ways that are still incompletely understood. Retroviral envelope glycoproteins interact with several host proteins, extracellularly with their cellular ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008605]

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RNF8 Dysregulation and Down-regulation During HTLV-1 Infection Promote Genomic Instability in Adult T-Cell Leukemia.

Huijun Zhi, Xin Guo, Yik-Khuan Ho, Nagesh Pasupala, Hampus Alexander Anders Engstrom, Oliver John Semmes, Chou-Zen Giam,

The genomic instability associated with adult T cell leukemia/lymphoma (ATL) is causally linked to Tax, the HTLV-1 viral oncoprotein, but the underlying mechanism is not fully understood. We have previously shown that Tax hijacks and aberrantly activates ring finger protein 8 (RNF8) - a lysine 63 (K63)-specific ubiquitin E3 ligase ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2020, 16(5):e1008618]

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