7,161 results match your criteria PLoS Pathogens [Journal]


Central memory CD8+ T cells become CD69+ tissue-residents during viral skin infection independent of CD62L-mediated lymph node surveillance.

PLoS Pathog 2019 Mar 15;15(3):e1007633. Epub 2019 Mar 15.

Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.

Memory CD8+ T cells in the circulation rapidly infiltrate non-lymphoid tissues following infection and provide protective immunity in an antigen-specific manner. However, the subsequent fate of memory CD8+ T cells after entering non-lymphoid tissues such as the skin during a secondary infection is largely unknown. Furthermore, because expression of CD62L is often used to identify the central memory (TCM) CD8+ T cell subset, uncoupling the physical requirement for CD62L-mediated lymph node homing versus other functional attributes of TCM CD8+ T cells remains unresolved. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007633DOI Listing

Host adaptation and convergent evolution increases antibiotic resistance without loss of virulence in a major human pathogen.

PLoS Pathog 2019 Mar 15;15(3):e1007218. Epub 2019 Mar 15.

Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, New South Wales, Australia.

As human population density and antibiotic exposure increase, specialised bacterial subtypes have begun to emerge. Arising among species that are common commensals and infrequent pathogens, antibiotic-resistant 'high-risk clones' have evolved to better survive in the modern human. Here, we show that the major matrix porin (OmpK35) of Klebsiella pneumoniae is not required in the mammalian host for colonisation, pathogenesis, nor for antibiotic resistance, and that it is commonly absent in pathogenic isolates. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007218DOI Listing

Varicella zoster virus productively infects human peripheral blood mononuclear cells to modulate expression of immunoinhibitory proteins and blocking PD-L1 enhances virus-specific CD8+ T cell effector function.

PLoS Pathog 2019 Mar 14;15(3):e1007650. Epub 2019 Mar 14.

Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.

Varicella zoster virus (VZV) is a lymphotropic alpha-herpesvirinae subfamily member that produces varicella on primary infection and causes zoster, vascular disease and vision loss upon reactivation from latency. VZV-infected peripheral blood mononuclear cells (PBMCs) disseminate virus to distal organs to produce clinical disease. To assess immune evasion strategies elicited by VZV that may contribute to dissemination of infection, human PBMCs and VZV-specific CD8+ T cells (V-CD8+) were mock- or VZV-infected and analyzed for immunoinhibitory protein PD-1, PD-L1, PD-L2, CTLA-4, LAG-3 and TIM-3 expression using flow cytometry. Read More

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http://dx.plos.org/10.1371/journal.ppat.1007650
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http://dx.doi.org/10.1371/journal.ppat.1007650DOI Listing
March 2019
2 Reads

Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice.

PLoS Pathog 2019 Mar 14;15(3):e1007617. Epub 2019 Mar 14.

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Rome, Italy.

Herpes simplex virus type 1 (HSV-1) is a DNA neurotropic virus, usually establishing latent infections in the trigeminal ganglia followed by periodic reactivations. Although numerous findings suggested potential links between HSV-1 and Alzheimer's disease (AD), a causal relation has not been demonstrated yet. Hence, we set up a model of recurrent HSV-1 infection in mice undergoing repeated cycles of viral reactivation. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007617DOI Listing

The small non-coding RNA RsaE influences extracellular matrix composition in Staphylococcus epidermidis biofilm communities.

PLoS Pathog 2019 Mar 14;15(3):e1007618. Epub 2019 Mar 14.

University of Würzburg, Institute of Molecular Infection Biology, Würzburg, Germany.

RsaE is a conserved small regulatory RNA (sRNA) which was previously reported to represent a riboregulator of central carbon flow and other metabolic pathways in Staphylococcus aureus and Bacillus subtilis. Here we show that RsaE contributes to extracellular (e)DNA release and biofilm-matrix switching towards polysaccharide intercellular adhesin (PIA) production in a hypervariable Staphylococcus epidermidis isolate. Transcriptome analysis through differential RNA sequencing (dRNA-seq) in combination with confocal laser scanning microscopy (CLSM) and reporter gene fusions demonstrate that S. Read More

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http://dx.plos.org/10.1371/journal.ppat.1007618
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http://dx.doi.org/10.1371/journal.ppat.1007618DOI Listing
March 2019
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The fungal ribonuclease-like effector protein CSEP0064/BEC1054 represses plant immunity and interferes with degradation of host ribosomal RNA.

PLoS Pathog 2019 Mar 11;15(3):e1007620. Epub 2019 Mar 11.

Department of Life Sciences, Imperial College London, London, United Kingdom.

The biotrophic fungal pathogen Blumeria graminis causes the powdery mildew disease of cereals and grasses. We present the first crystal structure of a B. graminis effector of pathogenicity (CSEP0064/BEC1054), demonstrating it has a ribonuclease (RNase)-like fold. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007620DOI Listing

Desialylation of platelets induced by Von Willebrand Factor is a novel mechanism of platelet clearance in dengue.

PLoS Pathog 2019 Mar 8;15(3):e1007500. Epub 2019 Mar 8.

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.

Thrombocytopenia and platelet dysfunction are commonly observed in patients with dengue virus (DENV) infection and may contribute to complications such as bleeding and plasma leakage. The etiology of dengue-associated thrombocytopenia is multifactorial and includes increased platelet clearance. The binding of the coagulation protein von Willebrand factor (VWF) to the platelet membrane and removal of sialic acid (desialylation) are two well-known mechanisms of platelet clearance, but whether these conditions also contribute to thrombocytopenia in dengue infection is unknown. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007500DOI Listing
March 2019
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Bile salt hydrolases: Gatekeepers of bile acid metabolism and host-microbiome crosstalk in the gastrointestinal tract.

PLoS Pathog 2019 Mar 7;15(3):e1007581. Epub 2019 Mar 7.

Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.

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http://dx.doi.org/10.1371/journal.ppat.1007581DOI Listing

Coincident airway exposure to low-potency allergen and cytomegalovirus sensitizes for allergic airway disease by viral activation of migratory dendritic cells.

PLoS Pathog 2019 Mar 7;15(3):e1007595. Epub 2019 Mar 7.

Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Despite a broad cell-type tropism, cytomegalovirus (CMV) is an evidentially pulmonary pathogen. Predilection for the lungs is of medical relevance in immunocompromised recipients of hematopoietic cell transplantation, in whom interstitial CMV pneumonia is a frequent and, if left untreated, fatal clinical manifestation of human CMV infection. A conceivable contribution of CMV to airway diseases of other etiology is an issue that so far attracted little medical attention. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007595DOI Listing
March 2019
2 Reads

Neisseria gonorrhoeae MlaA influences gonococcal virulence and membrane vesicle production.

PLoS Pathog 2019 Mar 7;15(3):e1007385. Epub 2019 Mar 7.

Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, United States of America.

The six-component maintenance of lipid asymmetry (Mla) system is responsible for retrograde transport of phospholipids, ensuring the barrier function of the Gram-negative cell envelope. Located within the outer membrane, MlaA (VacJ) acts as a channel to shuttle phospholipids from the outer leaflet. We identified Neisseria gonorrhoeae MlaA (ngo2121) during high-throughput proteomic mining for potential therapeutic targets against this medically important human pathogen. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007385DOI Listing

Intestinal Serum amyloid A suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization.

PLoS Pathog 2019 Mar 7;15(3):e1007381. Epub 2019 Mar 7.

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.

The intestinal microbiota influences the development and function of myeloid lineages such as neutrophils, but the underlying molecular mechanisms are unresolved. Using gnotobiotic zebrafish, we identified the immune effector Serum amyloid A (Saa) as one of the most highly induced transcripts in digestive tissues following microbiota colonization. Saa is a conserved secreted protein produced in the intestine and liver with described effects on neutrophils in vitro, however its in vivo functions remain poorly defined. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007381DOI Listing
March 2019
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Transmission phenotype of Mycobacterium tuberculosis strains is mechanistically linked to induction of distinct pulmonary pathology.

PLoS Pathog 2019 Mar 6;15(3):e1007613. Epub 2019 Mar 6.

Rutgers University-New Jersey Medical School, Department of Medicine, Centre for Emerging Pathogens, Newark, New Jersey, United States of America.

In a study of household contacts (HHC), households were categorized into High (HT) and Low (LT) transmission groups based on the proportion of HHC with a positive tuberculin skin test. The Mycobacterium tuberculosis (Mtb) strains from HT and LT index cases of the households were designated Mtb-HT and Mtb-LT, respectively. We found that C3HeB/FeJ mice infected with Mtb-LT strains exhibited significantly higher bacterial burden compared to Mtb-HT strains and also developed diffused inflammatory lung pathology. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007613DOI Listing

A comparison of antigen-specific T cell responses induced by six novel tuberculosis vaccine candidates.

PLoS Pathog 2019 Mar 4;15(3):e1007643. Epub 2019 Mar 4.

South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, Western Cape, South Africa.

Eradication of tuberculosis (TB), the world's leading cause of death due to infectious disease, requires a highly efficacious TB vaccine. Many TB vaccine candidates are in pre-clinical and clinical development but only a few can be advanced to large-scale efficacy trials due to limited global resources. We aimed to perform a statistically rigorous comparison of the antigen-specific T cell responses induced by six novel TB vaccine candidates and the only licensed TB vaccine, Bacillus Calmette-Guérin (BCG). Read More

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http://dx.doi.org/10.1371/journal.ppat.1007643DOI Listing
March 2019
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Structural roles of PCV2 capsid protein N-terminus in PCV2 particle assembly and identification of PCV2 type-specific neutralizing epitope.

PLoS Pathog 2019 Mar 1;15(3):e1007562. Epub 2019 Mar 1.

Department of Biological Sciences and Centre for Bioimaging Sciences, National University of Singapore, Singapore.

Postweaning multisystemic wasting disease (PMWS) in piglets caused by porcine circovirus type 2 (PCV2) is one of the major threats to most pig farms worldwide. Among all the PCV types, PCV2 is the dominant genotype causing PMWS and associated diseases. Considerable efforts were made to study the virus-like-particle (VLP) assembly and the specific PCV2-associated epitope(s) in order to establish the solid foundation for engineered PCV2 vaccine development. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007562DOI Listing

Sensing of cell-associated HTLV by plasmacytoid dendritic cells is regulated by dense β-galactoside glycosylation.

PLoS Pathog 2019 02 28;15(2):e1007589. Epub 2019 Feb 28.

CIRI-Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS Lyon, Lyon, France.

Human T Lymphotropic virus (HTLV) infection can persist in individuals resulting, at least in part, from viral escape of the innate immunity, including inhibition of type I interferon response in infected T-cells. Plasmacytoid dendritic cells (pDCs) are known to bypass viral escape by their robust type I interferon production. Here, we demonstrated that pDCs produce type I interferons upon physical cell contact with HTLV-infected cells, yet pDC activation inversely correlates with the ability of the HTLV-producing cells to transmit infection. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007589DOI Listing
February 2019

High-risk human papillomavirus oncogenes disrupt the Fanconi anemia DNA repair pathway by impairing localization and de-ubiquitination of FancD2.

PLoS Pathog 2019 02 28;15(2):e1007442. Epub 2019 Feb 28.

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

Persistent expression of high-risk HPV oncogenes is necessary for the development of anogenital and oropharyngeal cancers. Here, we show that E6/E7 expressing cells are hypersensitive to DNA crosslinking agent cisplatin and have defects in repairing DNA interstrand crosslinks (ICL). Importantly, we elucidate how E6/E7 attenuate the Fanconi anemia (FA) DNA crosslink repair pathway. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007442DOI Listing
February 2019
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Interleukin 21 collaborates with interferon-γ for the optimal expression of interferon-stimulated genes and enhances protection against enteric microbial infection.

PLoS Pathog 2019 02 28;15(2):e1007614. Epub 2019 Feb 28.

Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America.

The mucosal surface of the intestinal tract represents a major entry route for many microbes. Despite recent progress in the understanding of the IL-21/IL-21R signaling axis in the generation of germinal center B cells, the roles played by this signaling pathway in the context of enteric microbial infections is not well-understood. Here, we demonstrate that Il21r-/- mice are more susceptible to colonic microbial infection, and in the process discovered that the IL-21/IL-21R signaling axis surprisingly collaborates with the IFN-γ/IFN-γR signaling pathway to enhance the expression of interferon-stimulated genes (ISGs) required for protection, via amplifying activation of STAT1 in mucosal CD4+ T cells in a murine model of Citrobacter rodentium colitis. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007614DOI Listing
February 2019
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The selective autophagy receptors Optineurin and p62 are both required for zebrafish host resistance to mycobacterial infection.

PLoS Pathog 2019 02 28;15(2):e1007329. Epub 2019 Feb 28.

Institute of Biology Leiden, Leiden University, Leiden, The Netherlands.

Mycobacterial pathogens are the causative agents of chronic infectious diseases like tuberculosis and leprosy. Autophagy has recently emerged as an innate mechanism for defense against these intracellular pathogens. In vitro studies have shown that mycobacteria escaping from phagosomes into the cytosol are ubiquitinated and targeted by selective autophagy receptors. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007329DOI Listing
February 2019
3 Reads

Complete protection of the BALB/c and C57BL/6J mice against Ebola and Marburg virus lethal challenges by pan-filovirus T-cell epigraph vaccine.

PLoS Pathog 2019 02 28;15(2):e1007564. Epub 2019 Feb 28.

The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.

There are a number of vaccine candidates under development against a small number of the most common outbreak filoviruses all employing the virus glycoprotein (GP) as the vaccine immunogen. However, antibodies induced by such GP vaccines are typically autologous and limited to the other members of the same species. In contrast, T-cell vaccines offer a possibility to design a single pan-filovirus vaccine protecting against all known and even likely existing, but as yet unencountered members of the family. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394903PMC
February 2019
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Killing two birds with one stone: How the respiratory syncytial virus polymerase initiates transcription and replication.

PLoS Pathog 2019 02 28;15(2):e1007548. Epub 2019 Feb 28.

Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.

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http://dx.doi.org/10.1371/journal.ppat.1007548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394897PMC
February 2019

Colonization of the tsetse fly midgut with commensal Kosakonia cowanii Zambiae inhibits trypanosome infection establishment.

PLoS Pathog 2019 02 28;15(2):e1007470. Epub 2019 Feb 28.

Yale School of Public Health, Department of Epidemiology of Microbial Diseases, New Haven, Connecticut, United States of America.

Tsetse flies (Glossina spp.) vector pathogenic trypanosomes (Trypanosoma spp.) in sub-Saharan Africa. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394900PMC
February 2019
1 Read

PLOS Pathogens 2018 Reviewer and Editorial Board Thank You.

Authors:

PLoS Pathog 2019 02 27;15(2):e1007649. Epub 2019 Feb 27.

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http://dx.doi.org/10.1371/journal.ppat.1007649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392270PMC
February 2019

NDRG1 facilitates the replication and persistence of Kaposi's sarcoma-associated herpesvirus by interacting with the DNA polymerase clamp PCNA.

PLoS Pathog 2019 02 27;15(2):e1007628. Epub 2019 Feb 27.

State Key Laboratory of Virology, College of Life Sciences, Medical Research Institute, Wuhan University, Wuhan, China.

Kaposi's sarcoma-associated herpesvirus (KSHV) latently infects host cells and establishes lifelong persistence as an extra-chromosomal episome in the nucleus. To persist in proliferating cells, the viral genome typically replicates once per cell cycle and is distributed into daughter cells. This process involves host machinery utilized by KSHV, however the underlying mechanisms are not fully elucidated. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007628DOI Listing
February 2019

Single-cell characterization and quantification of translation-competent viral reservoirs in treated and untreated HIV infection.

PLoS Pathog 2019 02 27;15(2):e1007619. Epub 2019 Feb 27.

Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.

The phenotypic characterization of the cells in which HIV persists during antiretroviral therapy (ART) remains technically challenging. We developed a simple flow cytometry-based assay to quantify and characterize infected cells producing HIV proteins during untreated and treated HIV infection. By combining two antibodies targeting the HIV capsid in a standard intracellular staining protocol, we demonstrate that p24-producing cells can be detected with high specificity and sensitivity in the blood from people living with HIV. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007619DOI Listing
February 2019

Plasmodium-specific antibodies block in vivo parasite growth without clearing infected red blood cells.

PLoS Pathog 2019 02 27;15(2):e1007599. Epub 2019 Feb 27.

QIMR Berghofer Medical Research Institute, Herston, Brisbane QLD, Australia.

Plasmodium parasites invade and multiply inside red blood cells (RBC). Through a cycle of maturation, asexual replication, rupture and release of multiple infective merozoites, parasitised RBC (pRBC) can reach very high numbers in vivo, a process that correlates with disease severity in humans and experimental animals. Thus, controlling pRBC numbers can prevent or ameliorate malaria. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007599DOI Listing
February 2019
2 Reads

Modulation of calcium signaling pathway by hepatitis C virus core protein stimulates NLRP3 inflammasome activation.

PLoS Pathog 2019 02 27;15(2):e1007593. Epub 2019 Feb 27.

Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America.

Hepatitis C virus (HCV) infection remains a major cause of hepatic inflammation and liver disease. HCV triggers NLRP3 inflammasome activation and interleukin-1β (IL-1β) production from hepatic macrophages, or Kupffer cells, to drive the hepatic inflammatory response. Here we examined HCV activation of the NLRP3 inflammasome signaling cascade in primary human monocyte derived macrophages and THP-1 cell models of hepatic macrophages to define the HCV-specific agonist and cellular processes of inflammasome activation. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392285PMC
February 2019

The seven transmembrane domain protein MoRgs7 functions in surface perception and undergoes coronin MoCrn1-dependent endocytosis in complex with Gα subunit MoMagA to promote cAMP signaling and appressorium formation in Magnaporthe oryzae.

PLoS Pathog 2019 02 25;15(2):e1007382. Epub 2019 Feb 25.

Department of Plant Pathology, College of Plant Protection, Nanjing Agricultural University, and Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing, China.

Regulator of G-protein signaling (RGS) proteins primarily function as GTPase-accelerating proteins (GAPs) to promote GTP hydrolysis of Gα subunits, thereby regulating G-protein mediated signal transduction. RGS proteins could also contain additional domains such as GoLoco to inhibit GDP dissociation. The rice blast fungus Magnaporthe oryzae encodes eight RGS and RGS-like proteins (MoRgs1 to MoRgs8) that have shared and distinct functions in growth, appressorium formation and pathogenicity. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007382DOI Listing
February 2019

PML nuclear body-residing proteins sequentially associate with HPV genome after infectious nuclear delivery.

PLoS Pathog 2019 02 25;15(2):e1007590. Epub 2019 Feb 25.

Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.

Subnuclear promyelocytic leukemia (PML) nuclear bodies (NBs) are targeted by many DNA viruses after nuclear delivery. PML protein is essential for formation of PML NBs. Sp100 and Small Ubiquitin-Like Modifier (SUMO) are also permanently residing within PML NBs. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007590DOI Listing
February 2019
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The founder hypothesis: A basis for microbiota resistance, diversity in taxa carriage, and colonization resistance against pathogens.

PLoS Pathog 2019 02 21;15(2):e1007563. Epub 2019 Feb 21.

Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America.

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http://dx.doi.org/10.1371/journal.ppat.1007563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383860PMC
February 2019

Plant begomoviruses subvert ubiquitination to suppress plant defenses against insect vectors.

PLoS Pathog 2019 02 21;15(2):e1007607. Epub 2019 Feb 21.

Ministry of Agriculture Key Lab of Molecular Biology of Crop Pathogens and Insects, Institute of Insect Sciences, Zhejiang University, Hangzhou, China.

Most plant viruses are vectored by insects and the interactions of virus-plant-vector have important ecological and evolutionary implications. Insect vectors often perform better on virus-infected plants. This indirect mutualism between plant viruses and insect vectors promotes the spread of virus and has significant agronomical effects. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007607DOI Listing
February 2019
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Casting a wider net: Immunosurveillance by nonclassical MHC molecules.

PLoS Pathog 2019 02 21;15(2):e1007567. Epub 2019 Feb 21.

Laboratory of Viral Diseases, NIAID, Bethesda, Maryland, United States of America.

Most studies of T lymphocytes focus on recognition of classical major histocompatibility complex (MHC) class I or II molecules presenting oligopeptides, yet there are numerous variations and exceptions of biological significance based on recognition of a wide variety of nonclassical MHC molecules. These include αβ and γδ T cells that recognize different class Ib molecules (CD1, MR-1, HLA-E, G, F, et al.) that are nearly monomorphic within a given species. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383864PMC
February 2019
1 Read

Kaposi's sarcoma-associated herpesvirus ORF57 protein protects viral transcripts from specific nuclear RNA decay pathways by preventing hMTR4 recruitment.

PLoS Pathog 2019 02 20;15(2):e1007596. Epub 2019 Feb 20.

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas.

Nuclear RNAs are subject to a number of RNA decay pathways that serve quality control and regulatory functions. As a result, any virus that expresses its genes in the nucleus must have evolved mechanisms that avoid these pathways, but the how viruses evade nuclear RNA decay remains largely unknown. The multifunctional Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 (Mta) protein is required for the nuclear stability of viral transcripts. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398867PMC
February 2019
2 Reads

Identification of HIV gp41-specific antibodies that mediate killing of infected cells.

PLoS Pathog 2019 02 19;15(2):e1007572. Epub 2019 Feb 19.

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle WA, United States of America.

Antibodies that mediate killing of HIV-infected cells through antibody-dependent cellular cytotoxicity (ADCC) have been implicated in protection from HIV infection and disease progression. Despite these observations, these types of HIV antibodies are understudied compared to neutralizing antibodies. Here we describe four monoclonal antibodies (mAbs) obtained from one individual that target the HIV transmembrane protein, gp41, and mediate ADCC activity. Read More

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http://dx.plos.org/10.1371/journal.ppat.1007572
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http://dx.doi.org/10.1371/journal.ppat.1007572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396944PMC
February 2019
2 Reads

Atomic structures and deletion mutant reveal different capsid-binding patterns and functional significance of tegument protein pp150 in murine and human cytomegaloviruses with implications for therapeutic development.

PLoS Pathog 2019 02 19;15(2):e1007615. Epub 2019 Feb 19.

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, California, United States of America.

Cytomegalovirus (CMV) infection causes birth defects and life-threatening complications in immunosuppressed patients. Lack of vaccine and need for more effective drugs have driven widespread ongoing therapeutic development efforts against human CMV (HCMV), mostly using murine CMV (MCMV) as the model system for preclinical animal tests. The recent publication (Yu et al. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396938PMC
February 2019
2 Reads

Picornavirus infection induces temporal release of multiple extracellular vesicle subsets that differ in molecular composition and infectious potential.

PLoS Pathog 2019 02 19;15(2):e1007594. Epub 2019 Feb 19.

Department of Biochemistry & Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

Several naked virus species, including members of the Picornaviridae family, have recently been described to escape their host cells and spread infection via enclosure in extracellular vesicles (EV). EV are 50-300 nm sized lipid membrane-enclosed particles produced by all cells that are broadly recognized for playing regulatory roles in numerous (patho)physiological processes, including viral infection. Both pro- and antiviral functions have been ascribed to EV released by virus-infected cells. Read More

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http://dx.plos.org/10.1371/journal.ppat.1007594
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http://dx.doi.org/10.1371/journal.ppat.1007594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396942PMC
February 2019
3 Reads

EhFP10: A FYVE family GEF interacts with myosin IB to regulate cytoskeletal dynamics during endocytosis in Entamoeba histolytica.

PLoS Pathog 2019 02 19;15(2):e1007573. Epub 2019 Feb 19.

School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.

Motility and phagocytosis are key processes that are involved in invasive amoebiasis disease caused by intestinal parasite Entamoeba histolytica. Previous studies have reported unconventional myosins to play significant role in membrane based motility as well as endocytic processes. EhMyosin IB is the only unconventional myosin present in E. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396940PMC
February 2019

Human IFIT proteins inhibit lytic replication of KSHV: A new feed-forward loop in the innate immune system.

PLoS Pathog 2019 02 19;15(2):e1007609. Epub 2019 Feb 19.

Division of Infectious Diseases, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.

Kaposi's sarcoma-associated herpesvirus (KSHV) is causally associated with Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman's disease. The IFIT family of proteins inhibits replication of some viruses, but their effects on KSHV lytic replication was unknown. Here we show that KSHV lytic replication induces IFIT expression in epithelial cells. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396945PMC
February 2019

A poxvirus pseudokinase represses viral DNA replication via a pathway antagonized by its paralog kinase.

PLoS Pathog 2019 02 15;15(2):e1007608. Epub 2019 Feb 15.

Nebraska Center for Virology, University of Nebraska, Lincoln, NE, United States of America.

Poxviruses employ sophisticated, but incompletely understood, signaling pathways that engage cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. For example, the vaccinia B1 protein kinase plays a vital role in inactivating the cellular antiviral factor BAF, and likely orchestrates other pathways as well. In this study, we utilized experimental evolution of a B1 deletion virus to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395007PMC
February 2019
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Cyclical adaptation of measles virus quasispecies to epithelial and lymphocytic cells: To V, or not to V.

PLoS Pathog 2019 02 15;15(2):e1007605. Epub 2019 Feb 15.

Department of Molecular Medicine, Mayo Clinic, Rochester, MN, United States of America.

Measles virus (MeV) is dual-tropic: it replicates first in lymphatic tissues and then in epithelial cells. This switch in tropism raises the question of whether, and how, intra-host evolution occurs. Towards addressing this question, we adapted MeV either to lymphocytic (Granta-519) or epithelial (H358) cells. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395005PMC
February 2019
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A high rate of polymerization during synthesis of mouse mammary tumor virus DNA alleviates hypermutation by APOBEC3 proteins.

PLoS Pathog 2019 02 15;15(2):e1007533. Epub 2019 Feb 15.

Institute of Virology, University of Veterinary Medicine Vienna, Vienna, Austria.

Retroviruses have evolved multiple means to counteract host restriction factors such as single-stranded DNA-specific deoxycytidine deaminases (APOBEC3s, A3s). These include exclusion of A3s from virions by an A3-unreactive nucleocapsid or expression of an A3-neutralizing protein (Vif, Bet). However, a number of retroviruses package A3s and do not encode apparent vif- or bet-like genes, yet they replicate in the presence of A3s. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395001PMC
February 2019

The transcription factor NHR-8: A new target to increase ivermectin efficacy in nematodes.

PLoS Pathog 2019 02 13;15(2):e1007598. Epub 2019 Feb 13.

INTHERES, Université de Toulouse, INRA, ENVT, Toulouse, France.

Resistance to the anthelmintic macrocyclic lactone ivermectin (IVM) has a great impact on the control of parasitic nematodes. The mechanisms by which nematodes adapt to IVM remain to be deciphered. We have identified NHR-8, a nuclear hormone receptor involved in the xenobiotic response in Caenorhabditis elegans, as a new regulator of tolerance to IVM. Read More

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http://dx.plos.org/10.1371/journal.ppat.1007598
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http://dx.doi.org/10.1371/journal.ppat.1007598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391013PMC
February 2019
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Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes.

PLoS Pathog 2019 02 12;15(2):e1007495. Epub 2019 Feb 12.

BIO5 Institute, University of Arizona, Tucson, AZ, United States of America.

The Gram-negative human pathogen N. gonorrhoeae (Ngo) quickly attaches to epithelial cells, and large numbers of the bacteria remain on the cell surface for prolonged periods. Ngo invades cells but few viable intracellular bacteria are recovered until later stages of infection, leading to the assumption that Ngo is a weak invader. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388937PMC
February 2019

TDP-43 proteinopathy in Theiler's murine encephalomyelitis virus infection.

PLoS Pathog 2019 02 11;15(2):e1007574. Epub 2019 Feb 11.

Departments of Neurology, University of Chicago Medical Center, Chicago, IL, United States of America.

TDP-43, an RNA-binding protein that is primarily nuclear and important in splicing and RNA metabolism, is mislocalized from the nucleus to the cytoplasm of neural cells in amyotrophic lateral sclerosis (ALS), and contributes to disease. We sought to investigate whether TDP-43 is mislocalized in infections with the acute neuronal GDVII strain and the persistent demyelinating DA strain of Theiler's virus murine encephalomyelitis virus (TMEV), a member of the Cardiovirus genus of Picornaviridae because: i) L protein of both strains is known to disrupt nucleocytoplasmic transport, including transport of polypyrimidine tract binding protein, an RNA-binding protein, ii) motor neurons and oligodendrocytes are targeted in both TMEV infection and ALS. TDP-43 phosphorylation, cleavage, and cytoplasmic mislocalization to an aggresome were observed in wild type TMEV-infected cultured cells, with predicted splicing abnormalities. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390522PMC
February 2019
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The tyrosine transporter of Toxoplasma gondii is a member of the newly defined apicomplexan amino acid transporter (ApiAT) family.

PLoS Pathog 2019 02 11;15(2):e1007577. Epub 2019 Feb 11.

Research School of Biology, Australian National University, Canberra, ACT, Australia.

Apicomplexan parasites are auxotrophic for a range of amino acids which must be salvaged from their host cells, either through direct uptake or degradation of host proteins. Here, we describe a family of plasma membrane-localized amino acid transporters, termed the Apicomplexan Amino acid Transporters (ApiATs), that are ubiquitous in apicomplexan parasites. Functional characterization of the ApiATs of Toxoplasma gondii indicate that several of these transporters are important for intracellular growth of the tachyzoite stage of the parasite, which is responsible for acute infections. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386423PMC
February 2019

PolyGlcNAc-containing exopolymers enable surface penetration by non-motile Enterococcus faecalis.

PLoS Pathog 2019 02 11;15(2):e1007571. Epub 2019 Feb 11.

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, United States of America.

Bacterial pathogens have evolved strategies that enable them to invade tissues and spread within the host. Enterococcus faecalis is a leading cause of local and disseminated multidrug-resistant hospital infections, but the molecular mechanisms used by this non-motile bacterium to penetrate surfaces and translocate through tissues remain largely unexplored. Here we present experimental evidence indicating that E. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386517PMC
February 2019
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Rational design of a live-attenuated eastern equine encephalitis virus vaccine through informed mutation of virulence determinants.

PLoS Pathog 2019 02 11;15(2):e1007584. Epub 2019 Feb 11.

Center for Vaccine Research, Department of Immunology, University of Pittsburgh, Pittsburgh, PA United States of America.

Live attenuated vaccines (LAVs), if sufficiently safe, provide the most potent and durable anti-pathogen responses in vaccinees with single immunizations commonly yielding lifelong immunity. Historically, viral LAVs were derived by blind passage of virulent strains in cultured cells resulting in adaptation to culture and a loss of fitness and disease-causing potential in vivo. Mutations associated with these phenomena have been identified but rarely have specific attenuation mechanisms been ascribed, thereby limiting understanding of the attenuating characteristics of the LAV strain and applicability of the attenuation mechanism to other vaccines. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386422PMC
February 2019

The 14-3-3η chaperone protein promotes antiviral innate immunity via facilitating MDA5 oligomerization and intracellular redistribution.

PLoS Pathog 2019 02 11;15(2):e1007582. Epub 2019 Feb 11.

Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei City, Taiwan.

MDA5 belongs to the RIG-I-like receptor family and plays a non-redundant role in recognizing cytoplasmic viral RNA to induce the production of type I IFNs. Upon RNA ligand stimulation, we observed the redistribution of MDA5 from the cytosol to mitochondrial membrane fractions. However, the molecular mechanisms of MDA5 activation remain less understood. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386420PMC
February 2019

The switch between acute and persistent paramyxovirus infection caused by single amino acid substitutions in the RNA polymerase P subunit.

PLoS Pathog 2019 02 11;15(2):e1007561. Epub 2019 Feb 11.

School of Biology, Centre for Biomolecular Sciences, BMS Building, North Haugh, University of St. Andrews, St. Andrews, Fife, United Kingdom.

Paramyxoviruses can establish persistent infections both in vitro and in vivo, some of which lead to chronic disease. However, little is known about the molecular events that contribute to the establishment of persistent infections by RNA viruses. Using parainfluenza virus type 5 (PIV5) as a model we show that phosphorylation of the P protein, which is a key component of the viral RNA polymerase complex, determines whether or not viral transcription and replication becomes repressed at late times after infection. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386407PMC
February 2019