PLoS Pathogens最新文献_第5页

Molecular evolution and geographic migration of severe fever with thrombocytopenia syndrome virus in Asia.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-03-07 eCollection Date: 2025-03-01 DOI: 10.1371/journal.ppat.1012970

Ruyi Sheng, Tianyu Cheng, Yao Wang, Hongling Wen

{"title":"Molecular evolution and geographic migration of severe fever with thrombocytopenia syndrome virus in Asia.","authors":"Ruyi Sheng, Tianyu Cheng, Yao Wang, Hongling Wen","doi":"10.1371/journal.ppat.1012970","DOIUrl":"10.1371/journal.ppat.1012970","url":null,"abstract":"Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently identified tick-borne virus that has emerged in the twenty-first century. Its primary clinical manifestations include fever and thrombocytopenia, and its high morbidity and mortality rates have garnered significant attention. It is crucial to have a comprehensive understanding of the spatial and temporal characteristics of SFTSV migration in order to prevent and control this disease. The SFTSV strains from East Asian countries in GenBank during 2017-2023 were collected and analyzed with phylogenetic and Bayesian methods. Phylogenetic analysis showed that SFTSV can be categorized into five genotypes (A, B, C, D, and E), with 24 recombination events and 15 reassortment events identified. This represented a higher number than previously observed. The results of our study indicated that SFTSV first diverged around 1785. We categorized the migration of SFTSV into two distinct periods, and identified the centers of spread and migration routes of SFTSV in each period. We propose that the eastern migration routes of migratory birds played a pivotal role during the initial stages of virus transmission, functioning as a primary conduit for the dispersal of the virus across the sea. The eastern and central migratory routes were similarly pivotal in subsequent phases of virus transmission. The results of the study showed that Japan was the first region where the virus originated and became endemic, and that the virus spread widely among countries. Elucidating the spatial and temporal characteristics of SFTSV migration will help prevent and control SFTS.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1012970"},"PeriodicalIF":5.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Five things to consider before proposing that a circular RNA is a viroid.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-03-07 eCollection Date: 2025-03-01 DOI: 10.1371/journal.ppat.1012958

Jian Wu, David M Bisaro

引用次数: 0

Sporothrix is neglected among the neglected.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-03-06 eCollection Date: 2025-03-01 DOI: 10.1371/journal.ppat.1012898

Daniel R Matute, Marcus de Melo Teixeira

引用次数: 0

The CXCR6-CXCL16 axis mediates T cell control of polyomavirus infection in the kidney.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-03-05 eCollection Date: 2025-03-01 DOI: 10.1371/journal.ppat.1012969

Matthew D Lauver, Zoe E Katz, Havell Markus, Nicole M Derosia, Ge Jin, Katelyn N Ayers, Arrienne B Butic, Kaitlyn Bushey, Catherine S Abendroth, Dajiang J Liu, Aron E Lukacher

{"title":"The CXCR6-CXCL16 axis mediates T cell control of polyomavirus infection in the kidney.","authors":"Matthew D Lauver, Zoe E Katz, Havell Markus, Nicole M Derosia, Ge Jin, Katelyn N Ayers, Arrienne B Butic, Kaitlyn Bushey, Catherine S Abendroth, Dajiang J Liu, Aron E Lukacher","doi":"10.1371/journal.ppat.1012969","DOIUrl":"10.1371/journal.ppat.1012969","url":null,"abstract":"BK polyomavirus (PyV) establishes lifelong asymptomatic infections in the reno-urinary system of most humans. BKPyV-associated nephropathy is the leading infectious cause of kidney allograft loss. Using mouse PyV, a natural murine pathogen that also persists in the kidney, we define a dominant chemokine receptor-chemokine axis that directs T cell infiltration of the kidney. We found that CXCR6 was required for CD4+ and CD8+ T cells to be recruited to and retained in the kidney, respectively. Absence of CXCR6 impaired virus control in the kidney. The soluble form of CXCL16 was increased in kidneys of infected mice and in vivo CXCL16 neutralization reduced numbers of virus-specific CD8+ T cells infiltrating the kidney. In vivo administration of IL-12 upregulated CXCR6 expression on virus-specific CD8+ T cells, improved T cell recruitment to the infected kidney, and reduced virus levels. Notably, T cells in kidney biopsies from PyV-associated nephropathy patients express CXCR6 and transcriptional analysis shows significant upregulation of CXCR6 and CXCL16. These findings demonstrate the importance of the CXCR6-CXCL16 axis in regulating T cell responses in the kidney to PyV infection.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1012969"},"PeriodicalIF":5.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repurposing alcohol-abuse drug disulfiram for the treatment of KSHV-infected primary effusion lymphoma by activating antiviral innate immunity.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-03-04 eCollection Date: 2025-03-01 DOI: 10.1371/journal.ppat.1012957

Lijie Wang, Zhenshan Liu, Zeyu Xu, Wenjing Wang, Jinhong Yang, Junjie Zhang, Shanping He, Qiming Liang, Tingting Li

{"title":"Repurposing alcohol-abuse drug disulfiram for the treatment of KSHV-infected primary effusion lymphoma by activating antiviral innate immunity.","authors":"Lijie Wang, Zhenshan Liu, Zeyu Xu, Wenjing Wang, Jinhong Yang, Junjie Zhang, Shanping He, Qiming Liang, Tingting Li","doi":"10.1371/journal.ppat.1012957","DOIUrl":"10.1371/journal.ppat.1012957","url":null,"abstract":"Cancer remains a leading cause of global mortality, characterized by high treatment costs, and generally poor prognoses. Developing new anti-cancer drugs requires substantial investment, extended development timelines, and a high failure rate. Therefore, repurposing existing US Food and Drug Administration (FDA)-approved drugs for other diseases as potential anti-cancer therapies offers a faster and more cost-effective approach. Primary effusion lymphoma (PEL) is an aggressive B-cell malignancy linked to Kaposi's sarcoma-associated herpesvirus (KSHV) infection. In this study, we identified that disulfiram (DSF), an FDA-approved medication for alcohol dependence, acts as a potent inhibitor of KSHV-positive PEL. DSF suppresses PEL cell proliferation by inducing apoptosis through the activation of innate antiviral immunity. Remarkably, DSF effectively impedes KSHV reactivation and virion production in both PEL and endothelial cells. Inhibition of TANK binding kinase 1 (TBK1) or interferon regulatory factor 3 (IRF3), essential activators of antiviral innate immunity, reverses DSF's effects on PEL cell survival and KSHV reactivation. Furthermore, DSF treatment significantly hinders the initiation and progression of PEL tumors in a xenograft mouse model, with this effect was notably abolished by TBK1 depletion. Our findings highlighted DSF as a promising therapeutic agent for targeting persistent KSHV infection and treating PEL tumors.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1012957"},"PeriodicalIF":5.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A genome-wide screen in ex vivo gallbladders identifies Listeria monocytogenes factors required for virulence in vivo.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-03-03 eCollection Date: 2025-03-01 DOI: 10.1371/journal.ppat.1012491

Nicole H Schwardt, Cortney R Halsey, Madison E Sanchez, Billy M Ngo, Michelle L Reniere

{"title":"A genome-wide screen in ex vivo gallbladders identifies Listeria monocytogenes factors required for virulence in vivo.","authors":"Nicole H Schwardt, Cortney R Halsey, Madison E Sanchez, Billy M Ngo, Michelle L Reniere","doi":"10.1371/journal.ppat.1012491","DOIUrl":"10.1371/journal.ppat.1012491","url":null,"abstract":"Listeria monocytogenes is a Gram-positive pathogen that causes the severe foodborne disease listeriosis. Following oral infection of the host, L. monocytogenes disseminates from the gastrointestinal tract to peripheral organs, including the gallbladder, where it replicates to high densities, establishing the gallbladder as the primary bacterial reservoir. Despite its importance in pathogenesis, little is known about how L. monocytogenes survives and replicates in the gallbladder. In this study, we assessed the L. monocytogenes genes required for growth and survival in ex vivo non-human primate gallbladders using a transposon sequencing approach. The screen identified 43 genes required for replication in the gallbladder, some of which were known to be important for virulence, and others had not been previously studied in the context of infection. We evaluated the roles of 19 genes identified in our screen both in vitro and in vivo, and demonstrate that most were required for replication in bile in vitro, for intracellular infection of murine cells in tissue culture, and for virulence in an oral murine model of listeriosis. Interestingly, strains lacking the mannose and glucose phosphoenolpyruvate-dependent phosphotransferase system (PTS) permeases Mpt and Mpo exhibited no defects in intracellular growth or intercellular spread, but were significantly attenuated during murine infection. While the roles of PTS systems in vivo were not previously appreciated, these results suggest that PTS permeases are necessary for extracellular replication during infection. Overall, this study demonstrates that L. monocytogenes genes required for replication in the gallbladder also play broader roles in disease.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1012491"},"PeriodicalIF":5.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Understanding Mycobacterium tuberculosis through its genomic diversity and evolution.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-02-28 eCollection Date: 2025-02-01 DOI: 10.1371/journal.ppat.1012956

Mollie I Sweeney, Carson E Carranza, David M Tobin

{"title":"Understanding Mycobacterium tuberculosis through its genomic diversity and evolution.","authors":"Mollie I Sweeney, Carson E Carranza, David M Tobin","doi":"10.1371/journal.ppat.1012956","DOIUrl":"10.1371/journal.ppat.1012956","url":null,"abstract":"Pathogen evolution and genomic diversity are shaped by specific host immune pressures and therapeutic interventions. Analysis of the extant genomes of circulating strains of Mycobacterium tuberculosis, a leading cause of infectious mortality that has co-evolved with humans for thousands of years, can provide new insights into host-pathogen interactions that underlie specific aspects of pathogenesis and onward transmission. With the explosion in the number of fully sequenced M. tuberculosis strains that are now paired with detailed clinical data, there are new opportunities to understand the evolutionary basis for and consequences of M. tuberculosis strain diversity. This review examines mechanistic findings that have emerged from pairing whole genome sequencing data and evolutionary analysis with functional dissection of specific bacterial variants. These include improved understanding of secreted effectors that modulate the properties and migratory behavior of infected macrophages as well as bacterial genetic alterations important for survival within hypoxic microenvironments. Genomic, evolutionary, and functional analyses across diverse M. tuberculosis strains will identify prominent bacterial adaptations to their human hosts and shape our understanding of TB disease biology and the host immune response.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 2","pages":"e1012956"},"PeriodicalIF":5.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liver stage P. falciparum antigens highly targeted by CD4+ T cells in malaria-exposed Ugandan children.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-02-24 eCollection Date: 2025-02-01 DOI: 10.1371/journal.ppat.1012943

Gonzalo R Acevedo, Sophie S Samiee, Mikias Ilala, Justine Levan, Meagan E Olive, Riana D Hunter, Mary Prahl, Raja Rajalingam, John Rek, Grant Dorsey, Margaret E Feeney

{"title":"Liver stage P. falciparum antigens highly targeted by CD4+ T cells in malaria-exposed Ugandan children.","authors":"Gonzalo R Acevedo, Sophie S Samiee, Mikias Ilala, Justine Levan, Meagan E Olive, Riana D Hunter, Mary Prahl, Raja Rajalingam, John Rek, Grant Dorsey, Margaret E Feeney","doi":"10.1371/journal.ppat.1012943","DOIUrl":"10.1371/journal.ppat.1012943","url":null,"abstract":"T cell responses against liver stage Plasmodium help protect against reinfection, but the antigens and epitopes targeted by these T cells are largely unknown. This knowledge gap has impeded mechanistic studies to identify the effector functions most critical for protection. We performed a bioinformatic analysis of gene expression datasets to identify plasmodial genes that are highly and selectively expressed during liver stage infection and predict epitopes within them likely to bind MHC-II molecules prevalent in Uganda. We then tested their recognition by malaria-exposed Ugandan children. In over two-thirds of the children, we detected a peripheral blood CD4+ T cell response to one or more antigens. The most highly targeted antigen, LISP1, contained several epitopes, including one that was promiscuously presented and recognized by most participants. These novel liver stage P. falciparum epitopes should be explored as potential vaccine targets and will facilitate the development of tools to interrogate antimalarial immunity at the single-cell level and inform future vaccine development efforts.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 2","pages":"e1012943"},"PeriodicalIF":5.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Citrus tristeza virus p20 suppresses antiviral RNA silencing by co-opting autophagy-related protein 8 to mediate the autophagic degradation of SGS3. 柑橘三尖杉病毒 p20 通过与自噬相关蛋白 8 合作，介导 SGS3 的自噬降解，从而抑制抗病毒 RNA 沉默。

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-02-24 eCollection Date: 2025-02-01 DOI: 10.1371/journal.ppat.1012960

Yongle Zhang, Zuokun Yang, Zhe Zhang, Guoping Wang, Xiang-Dong Li, Ni Hong

{"title":"Citrus tristeza virus p20 suppresses antiviral RNA silencing by co-opting autophagy-related protein 8 to mediate the autophagic degradation of SGS3.","authors":"Yongle Zhang, Zuokun Yang, Zhe Zhang, Guoping Wang, Xiang-Dong Li, Ni Hong","doi":"10.1371/journal.ppat.1012960","DOIUrl":"10.1371/journal.ppat.1012960","url":null,"abstract":"Viruses exploit autophagy to degrade host immune components for their successful infection. However, how viral factors sequester the autophagic substrates into autophagosomes remains largely unknown. In this study, we showed that p20 protein, a viral suppressor of RNA silencing (VSR) encoded by citrus tristeza virus (CTV), mediated autophagic degradation of SUPPRESSOR OF GENE SILENCING 3 (SGS3), a plant-specific RNA-binding protein that is pivotal in antiviral RNA silencing. CTV infection activated autophagy, and the overexpression of p20 was sufficient to induce autophagy. Silencing of autophagy-related genes NbATG5 and NbATG7 attenuated CTV infection in Nicotiana benthamiana plants. In contrast, knockdown of the autophagy negative-regulated genes NbGAPCs led to virus accumulation, indicating the proviral role of autophagy in CTV infection. Further investigation found that p20 interacted with autophagy-related protein ATG8 through two ATG8-interacting motifs (AIMs) and sequestered SGS3 into autophagosomes by forming the ATG8-p20-SGS3 ternary complex. The mutations of the two AIMs in p20 (p20mAIM1 and p20mAIM5) abolished the interaction of p20 with ATG8, resulting in the deficiency of autophagy induction, SGS3 degradation, and VSR activity. Consistently, N. benthamiana plants infected with mutated CTVmAIM1 and CTVmAIM5 showed milder symptoms and decreased viral accumulation. Taken together, this study uncovers the molecular mechanism underlying how a VSR mediates the interplay between RNA silencing and autophagy to enhance the infection of a closterovirus.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 2","pages":"e1012960"},"PeriodicalIF":5.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interaction of the endogenous antibody response with activating FcγRs enhance control of Mayaro virus through monocytes.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-02-24 eCollection Date: 2025-02-01 DOI: 10.1371/journal.ppat.1012944

Megan M Dunagan, Nathânia Dábilla, Colton McNinch, Jason M Brenchley, Patrick T Dolan, Julie M Fox

{"title":"Interaction of the endogenous antibody response with activating FcγRs enhance control of Mayaro virus through monocytes.","authors":"Megan M Dunagan, Nathânia Dábilla, Colton McNinch, Jason M Brenchley, Patrick T Dolan, Julie M Fox","doi":"10.1371/journal.ppat.1012944","DOIUrl":"10.1371/journal.ppat.1012944","url":null,"abstract":"Mayaro virus (MAYV) is an emerging arbovirus. Previous studies have shown antibody Fc effector functions are critical for optimal monoclonal antibody-mediated protection against alphaviruses; however, the requirement of Fc gamma receptors (FcγRs) for protection during natural infection has not been evaluated. Here, we showed mice lacking activating FcγRs (FcRγ-/-) developed prolonged clinical disease with increased MAYV in joint-associated tissues. Viral reduction was associated with anti-MAYV cell surface binding antibodies rather than neutralizing antibodies. Lack of Fc-FcγR engagement increased the number of monocytes present in the joint-associated tissue through chronic timepoints. Single-cell RNA sequencing showed elevated levels of pro-inflammatory monocytes in joint-associated tissue with increased MAYV RNA present in FcRγ-/- monocytes and macrophages. Transfer of FcRγ-/- monocytes into wild type animals was sufficient to increase virus in joint-associated tissue. Overall, this study suggests that engagement of antibody Fc with activating FcγRs promotes protective responses during MAYV infection and prevents a pro-viral role for monocytes.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 2","pages":"e1012944"},"PeriodicalIF":5.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0