PLoS Pathogens最新文献

{"title":"An insect symbiotic virus promotes the transmission of a phytoarbovirus via inhibiting E3 ubiquitin ligase Sina.","authors":"Hui Wang, Jieting Zhang, Runfa Liu, You Li, Yu Du, Taiyun Wei","doi":"10.1371/journal.ppat.1013178","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013178","url":null,"abstract":"<p><p>Co-infection with symbiotic viruses and arboviruses with synergistic effects in insect vectors are common in nature, but the underlying mechanism remains elusive. Here, we identify a novel symbiotic virus, leafhopper Recilia dorsalis bunyavirus (RdBV), which enhances the transmission efficiency of cytorhabdovirus rice stripe mosaic virus (RSMV, a plant rhabdovirus) in field. RSMV infection activates the expression of R. dorsalis E3 ubiquitin ligase Seven in absentia (RdSina), while RdBV infection suppresses its expression. We show that RdSina directly targets and mediates the degradation of RSMV phosphoprotein (P), thereby attenuating the formation of P-induced viroplasm that are crucial for viral replication. RdSina interacts with nonstructural protein NSs2 of RdBV but does not mediate its ubiquitination. However, NSs2 competes with RSMV P for binding to RdSina, thus neutralizing RdSina's ability in mediating P degradation. Furthermore, we find that the MYC transcription factor binds to the promoter sequences of RdSina, activating its transcription. However, NSs2 also directly binds to the same promoter sequences of RdSina and competitively suppresses MYC-activated RdSina transcription. Together, NSs2 obstructs the function of RdSina in mediating P degradation, ultimately promoting RSMV propagation in co-infected vectors. These findings elucidate how insect symbiotic viruses negatively regulate E3 ubiquitin ligases to benefit arbovirus transmission by co-infected insect vectors, which potentially is a common phenomenon in nature.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 5","pages":"e1013178"},"PeriodicalIF":5.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181519","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}

{"title":"Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-like antibodies.","authors":"Parul Agrawal, Arineh Khechaduri, Kelsey R Salladay, Anna MacCamy, Duncan K Ralph, Andrew Riker, Andrew B Stuart, Latha Kallur Siddaramaiah, Xiaoying Shen, Frederick A Matsen, David Montefiori, Leonidas Stamatatos","doi":"10.1371/journal.ppat.1013039","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013039","url":null,"abstract":"<p><p>Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisition in two phase 2b efficacy trials. VRC01-class antibodies are therefore expected to be one component of an effective HIV-1 vaccine elicited response. In contrast to the VRC01-class antibodies that are highly mutated, their unmutated forms do not engage HIV-1 envelope (Env) and do not display neutralizing activities. Hence, specifically modified Env-derived proteins have been designed to engage the unmutated forms of VRC01-class antibodies, and to activate the corresponding naïve B cells. Selected heterologous Env must then be used as boost immunogens to guide the proper maturation of these elicited VRC01-class antibodies. Here we examined whether and how the valency of the prime and boost immunogens influences VRC01-class antibody-maturation. Our findings indicate that, indeed the valency of the immunogen affects the maturation of elicited antibody responses by preferentially selecting VRC01-like antibodies that have accumulated somatic mutations present in broadly neutralizing VRC01-class antibodies isolated from PLWH. As a result, antibodies isolated from animals immunized with the higher valency immunogens display broader Env cross-binding properties and improved neutralizing potentials than those isolated from animals immunized with the lower valency immunogens. Our results are relevant to current and upcoming phase 1 clinical trials that evaluate the ability of novel immunogens aiming to elicit cross-reactive VRC01-class antibody responses.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 5","pages":"e1013039"},"PeriodicalIF":5.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182481","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}

{"title":"Sentinels tracking viruses in various ecosystems: Towards a One Health approach.","authors":"Léo Blondet, Amour Mouanda Sounda, Matthieu Fritz, Denis Filloux, Michel Yvon, Stéphane Blanc, Arvind Varsani, Roch Fabien Niama, Eric M Leroy, Philippe Roumagnac","doi":"10.1371/journal.ppat.1013141","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013141","url":null,"abstract":"","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 5","pages":"e1013141"},"PeriodicalIF":5.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175461","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}

{"title":"Coxiella burnetii as a model system for understanding host immune response against obligate intracellular, vacuolar pathogens.","authors":"Akhila Sasikala, Chandhana Prakash, Mullai Valli Ramamoorthy, Sandhya Ganesan","doi":"10.1371/journal.ppat.1013071","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013071","url":null,"abstract":"","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 5","pages":"e1013071"},"PeriodicalIF":5.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175457","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}

{"title":"TRIM14 restricts tembusu virus infection through degrading viral NS1 protein and activating type I interferon signaling.","authors":"Peng Zhou, Qingxiang Zhang, Yueshan Yang, Dan Liu, Wanrong Wu, Anan Jongkaewwattana, Hui Jin, Hongbo Zhou, Rui Luo","doi":"10.1371/journal.ppat.1013200","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013200","url":null,"abstract":"<p><p>Tembusu virus (TMUV), an emerging avian orthoflavivirus, causes severe economic losses due to egg-drop syndrome and fatal encephalitis in domestic waterfowl. To combat this threat, the host immune system plays a crucial role in controlling and eliminating TMUV infection. Understanding the mechanisms of this immune response is thus vital for developing effective strategies against the virus. In this study, we investigated the antiviral activities of duck TRIM family proteins (duTRIM) against TMUV, focusing particularly on duTRIM14 as a potent host restriction factor. We showed that overexpression of duTRIM14 significantly inhibits TMUV replication, while its deficiency leads to increased viral titers. We elucidate a novel mechanism by which duTRIM14 interacts with the TMUV NS1 protein, facilitating its K27/K29-linked polyubiquitination and subsequent proteasomal degradation. The Lys141 residue on NS1 was identified as critical for this process, with its removal significantly enhancing TMUV replication both in vitro and in vivo. Furthermore, we showed that duTRIM14 interacts with duck TBK1 (duTBK1), promoting its K63-linked polyubiquitination on Lys30 and Lys401, which substantially augments IFN-β production during TMUV infection. Taken together, these results provide a novel dual-action antiviral mechanism in which duTRIM14 suppresses TMUV replication by simultaneously promoting proteasomal degradation of NS1 and enhancing the host antiviral response by modulating duTBK1 activity.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 5","pages":"e1013200"},"PeriodicalIF":5.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175463","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}

{"title":"Adaptive morphological changes link to poor clinical outcomes by conferring echinocandin tolerance in Candida tropicalis.","authors":"Yongqin Wu, Yun Zou, Yuanyuan Dai, Huaiwei Lu, Wei Zhang, Wenjiao Chang, Ying Wang, Zhengchao Nie, Yuanyuan Wang, Xiaohua Jiang","doi":"10.1371/journal.ppat.1013220","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013220","url":null,"abstract":"<p><p>Antibiotic tolerance, by which susceptible bacteria survive at high bactericide doses, is known to cause treatment failure in clinical practice. However, the impact of antifungal tolerance on clinical outcomes remains poorly understood. Here, we observed that candidemia cases caused by echinocandin-tolerant Candida tropicalis exhibited higher mortality rates during caspofungin treatment by conducting a comprehensive seven-year retrospective analysis. C. tropicalis develops tolerance to caspofungin by forming multicellular aggregates, a process linked to defects in cell division, both in vitro and in vivo. Our omics-based profiling results reveal that C. tropicalis develops tolerance through the intricate modulation of cell wall integrity and cell division pathways, particularly through the activation of chitin synthesis and the downregulation of cell division-related genes. The overexpression of cell division-related factor Ace2 can suppress the tolerance of C. tropicalis to caspofungin by delaying the formation of multicellular aggregates. Moreover, calcineurin inhibitors can suppress the tolerance of C. tropicalis by disrupting these adaptive molecular changes, thereby significantly enhancing the antifungal efficacy of caspofungin in a Galleria mellonella model. Collectively, our findings provide evidence that C. tropicalis acquires echinocandin tolerance through morphological alterations, and that inhibiting calcineurin may be a promising method to reduce this tolerance.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 5","pages":"e1013220"},"PeriodicalIF":5.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162555","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}

{"title":"The polyadenylase PAPI is required for virulence plasmid maintenance in pathogenic bacteria.","authors":"Katherine Schubert, Jessica Zhang, Michele E Muscolo, Micah Braly, Joshua W McCausland, Hanh N Lam, Karen Hug, Matthew Loven, Santiago Ruiz Solis, Melissa Estrada Escobar, Henry Moore, Derfel Terciano, Diana Fernandez Pacheco, Todd M Lowe, Cammie F Lesser, Christine Jacobs-Wagner, Helen Wang, Victoria Auerbuch","doi":"10.1371/journal.ppat.1012655","DOIUrl":"https://doi.org/10.1371/journal.ppat.1012655","url":null,"abstract":"<p><p>Many species of pathogenic bacteria harbor critical plasmid-encoded virulence factors, and yet the regulation of plasmid replication is often poorly understood despite playing a key role in plasmid-encoded gene expression. Human pathogenic Yersinia, including the plague agent Yersinia pestis and its close relative Y. pseudotuberculosis, require the type III secretion system (T3SS) virulence factor to subvert host defense mechanisms and colonize host tissues. The Yersinia T3SS is encoded on the IncFII plasmid for Yersinia virulence (pYV). Several layers of gene regulation enable a large increase in expression of Yersinia T3SS genes at mammalian body temperature. Surprisingly, T3SS expression is also controlled at the level of gene dosage. The number of pYV molecules relative to the number of chromosomes per cell, referred to as plasmid copy number, increases with temperature. The ability to increase and maintain elevated pYV plasmid copy number, and therefore T3SS gene dosage, at 37˚C is important for Yersinia virulence. In addition, pYV is highly stable in Yersinia at all temperatures, despite being dispensable for growth outside the host. Yet how Yersinia reinforces elevated plasmid replication and plasmid stability remains unclear. In this study, we show that the chromosomal gene pcnB encoding the polyadenylase PAP I is required for regulation of pYV plasmid copy number (PCN), maintenance of pYV in the bacterial population outside the host, robust T3SS activity, and Yersinia virulence in a mouse infection model. Likewise, pcnB/PAP I is required for robust expression of the Shigella flexneri T3SS that, similar to Yersinia, is encoded on a virulence plasmid whose replication is regulated by sRNA. Furthermore, Yersinia and Shigella pcnB/PAP I is required for maintaining model antimicrobial resistance (AMR) plasmids whose replication is regulated by sRNA, thereby increasing antibiotic resistance by ten-fold. These data suggest that pcnB/PAP I contributes to the spread and stabilization of sRNA-regulated virulence and AMR plasmids in bacterial pathogens, and is essential in maintaining the gene dosage required to mediate plasmid-encoded traits. Importantly pcnB/PAP I has been bioinformatically identified in many species of bacteria despite being studied in only a few species to date. Our work highlights the potential importance of pcnB/PAP I in antibiotic resistance, and shows for the first time that pcnB/PAP I promotes virulence plasmid stability in natural pathogenic hosts with a direct impact on bacterial virulence.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 5","pages":"e1012655"},"PeriodicalIF":5.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162597","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}

{"title":"Long lived liver-resident memory T cells of biased specificities for abundant sporozoite antigens drive malaria protection by radiation-attenuated sporozoite vaccination.","authors":"Maria N de Menezes, Zhengyu Ge, Anton Cozijnsen, Stephanie Gras, Patrick Bertolino, Irina Caminschi, Mireille H Lahoud, Katsuyuki Yui, Geoffrey I McFadden, Lynette Beattie, William R Heath, Daniel Fernandez-Ruiz","doi":"10.1371/journal.ppat.1012731","DOIUrl":"https://doi.org/10.1371/journal.ppat.1012731","url":null,"abstract":"<p><p>Vaccination with radiation-attenuated sporozoites (RAS) can provide highly effective protection against malaria in both humans and mice. To extend understanding of malaria immunity and inform the development of future vaccines, we studied the protective response elicited by this vaccine in C57BL/6 mice. We reveal that successive doses of Plasmodium berghei RAS favour the generation of liver CD8+ tissue-resident memory T cells (TRM cells) over circulating memory cells and markedly enhance their longevity. Importantly, RAS immunisation strongly skews the composition of the liver CD8+ TRM compartment towards cells specific for abundant sporozoite antigens, such as thrombospondin-related adhesive protein (TRAP) and circumsporozoite protein (CSP), which become major mediators of protection. The increased prevalence of sporozoite specificities is associated with limited intrahepatic attenuated parasite development and inhibition of naïve T cell responses to all parasite antigens, whether previously encountered or not, in previously vaccinated mice. This leads to the exclusive expansion of effector T cells formed upon initial immunisation, ultimately reducing the diversity of the liver TRM pool later established. However, stronger responses to less abundant epitopes can be achieved with higher initial doses of RAS. These findings provide novel insights into the mechanisms governing malaria immunity induced by attenuated sporozoite vaccination and highlight the susceptibility of this vaccine to limitations imposed by strain-specific immunity associated with the abundant, yet highly variable sporozoite antigens CSP and TRAP.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 5","pages":"e1012731"},"PeriodicalIF":5.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162556","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}

{"title":"Enteropathogenic Escherichia coli induces Entamoeba histolytica superdiffusion movement on fibronectin by reducing traction forces.","authors":"Yuanning Guo, Jun Ye, Ariel Shemesh, Anas Odeh, Meirav Trebicz-Geffen, Haguy Wolfenson, Serge Ankri","doi":"10.1371/journal.ppat.1012618","DOIUrl":"https://doi.org/10.1371/journal.ppat.1012618","url":null,"abstract":"<p><p>Amebiasis, caused by Entamoeba histolytica, is a global health concern, affecting millions and causing significant mortality, particularly in areas with poor sanitation. Although recent studies have examined E. histolytica's interaction with human intestinal microbes, the impact of bacterial presence on the parasite's motility, mechanical forces, and their potential role in altering invasiveness have not been fully elucidated. In this study, we utilized a micropillar-array system combined with live imaging to investigate the effects of enteropathogenic Escherichia coli on E. histolytica's motility characteristics, F-actin spatial localization, and traction force exerted on fibronectin-coated substrates. Our findings indicate that co-incubation with live enteropathogenic E. coli significantly enhances the motility of E. histolytica, as evidenced by superdiffusive movement-characterized by increased directionality and speed-resulting in broader dispersal and more extensive tissue/cell damage. This increased motility is accompanied by a reduction in F-actin-dependent traction forces and podosome-like structures on fibronectin-coated substrates, but with increased F-actin localization in the upper part of the cytoplasm. These findings highlight the role of physical interactions and cellular behaviors in modulating the parasite's virulence, providing new insights into the mechanistic basis of its pathogenicity.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 5","pages":"e1012618"},"PeriodicalIF":5.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133347","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}

{"title":"Stylet cuticular gene-directed mutagenesis impairs the pea aphid vector capacity to transmit a plant virus.","authors":"Yu Fu, Maëlle Deshoux, Bastien Cayrol, Sophie Le Blaye, Emma Achard, Sylvie Hudaverdian, Romuald Cloteau, Elodie Pichon, Elian Strozyk, Nathalie Prunier-Leterme, Emmanuelle Jousselin, Nicolas Sauvion, Gaël Thébaud, Gaël Le Trionnaire, Stefano Colella, Marilyne Uzest","doi":"10.1371/journal.ppat.1013192","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013192","url":null,"abstract":"<p><p>Aphids are major agricultural pests, notably because they transmit nearly 30% of known plant viruses, including non-circulative ones. They can be collected and dispersed rapidly among crops while aphids feed on infected plants. Most of these viruses are retained on receptors located on the cuticle of the stylet tip. The acrostyle, a cuticular micro-territory at the apex of aphid stylets, has been identified for its ability to retain the cauliflower mosaic virus (CaMV). The acrostyle displays cuticular proteins, known as stylins, with exposed domains accessible at the virus-vector interface. RNAi-mediated silencing of Stylin-01 designated this protein as the prime candidate receptor of CaMV. However, the results were incomplete due to the transient effect and highlighted the need for s mutants to advance our knowledge and validate these putative virus receptors. Here, we characterized the phenotype of two pea aphid Stylin-01 mutant lines, the first generated with CRISPR/Cas9 in this hemipteran. We showed that Stylin-01 mutations significantly disrupt CaMV transmission and impair the acrostyle's ability to bind the CaMV helper protein P2. Stylin-01 mutations also reshape the distribution of other stylins on the surface of mutant aphid stylets. In addition, Stylin-02, the putative ortholog of Stylin-01, is overexpressed in the mutant lines, pointing out a potential partial complementation of Stylin-01 in its structural role but not for virus transmission. In conclusion, this study, using the first stable aphid mutant lines, allows the characterization of the central role of Stylin-01 virus receptor in CaMV transmission.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 5","pages":"e1013192"},"PeriodicalIF":5.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133349","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}