PLoS Pathogens最新文献

{"title":"High pathogenicity avian influenza virus emergence: Blame it on chickens or on humans raising chickens?","authors":"Juliette Gross, Romain Volmer, Pierre Bessière","doi":"10.1371/journal.ppat.1012608","DOIUrl":"10.1371/journal.ppat.1012608","url":null,"abstract":"","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 10","pages":"e1012608"},"PeriodicalIF":5.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478576","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}

{"title":"8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus.","authors":"Lang Pan, Ke Wang, Wenjing Hao, Yaoyao Xue, Xu Zheng, Ritwika S Basu, Tapas K Hazra, Azharul Islam, Yashoda Hosakote, Bing Tian, Matthieu G Gagnon, Xueqing Ba, Istvan Boldogh","doi":"10.1371/journal.ppat.1012616","DOIUrl":"10.1371/journal.ppat.1012616","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV), along with other prominent respiratory RNA viruses such as influenza and SARS-CoV-2, significantly contributes to the global incidence of respiratory tract infections. These pathogens induce the production of reactive oxygen species (ROS), which play a crucial role in the onset and progression of respiratory diseases. However, the mechanisms by which viral RNA manages ROS-induced base oxidation remain poorly understood. Here, we reveal that 8-oxo-7,8-dihydroguanine (8-oxoGua) is not merely an incidental byproduct of ROS activity but serves as a strategic adaptation of RSV RNA to maintain genetic fidelity by hijacking the 8-oxoguanine DNA glycosylase 1 (OGG1). Through RNA immunoprecipitation and next-generation sequencing, we discovered that OGG1 binding sites are predominantly found in the RSV antigenome, especially within guanine-rich sequences. Further investigation revealed that viral ribonucleoprotein complexes specifically exploit OGG1. Importantly, inhibiting OGG1's ability to recognize 8-oxoGua significantly decreases RSV progeny production. Our results underscore the viral replication machinery's adaptation to oxidative challenges, suggesting that inhibiting OGG1's reading function could be a novel strategy for antiviral intervention.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 10","pages":"e1012616"},"PeriodicalIF":5.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478567","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}

{"title":"High phenotypic diversity correlated with genomic variation across the European Batrachochytrium salamandrivorans epizootic.","authors":"Moira Kelly, Christina A Cuomo, Wouter Beukema, Salvador Carranza, Jesse Erens, Marleen Foubert, Zhimin Li, Stefan Lötters, Vanessa Schulz, Sebastian Steinfartz, Sarah Van Praet, Michael Veith, Frank Pasmans, An Martel","doi":"10.1371/journal.ppat.1012579","DOIUrl":"10.1371/journal.ppat.1012579","url":null,"abstract":"<p><p>Recognizing the influence of pathogen diversity on infection dynamics is crucial for mitigating emerging infectious diseases. Characterising such diversity is often complex, for instance when multiple pathogen variants exist that interact differently with the environment and host. Here, we explore genotypic and phenotypic variation of Batrachochytrium salamandrivorans (Bsal), an emerging fungal pathogen that is driving declines among an increasing number of European amphibian species. For thirteen isolates, spanning most of the known temporal and geographical Bsal range in Europe, we mapped phenotypic diversity through numerous measurements that describe varying reproductive rates in vitro across a range of temperatures. Bsal isolates are revealed to have different thermal optima and tolerances, with phenotypic variation correlating with genomic diversity. Using a mechanistic niche model of the fire salamander (Salamandra salamandra) as an example, we illustrate how host steady-state body temperature and Bsal thermal range variation may influence pathogen growth through space and time across Europe. Our combined findings show how the identity of emergent pathogen variants may strongly influence when and which host populations are most at risk.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 10","pages":"e1012579"},"PeriodicalIF":5.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478577","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}

{"title":"Swine NONO promotes IRF3-mediated antiviral immune response by Detecting PRRSV N protein.","authors":"Dandan Jiang, Chao Sui, Xiangju Wu, Ping Jiang, Juan Bai, Yue Hu, Xiaoyan Cong, Juntong Li, Dongwan Yoo, Laura C Miller, Changhee Lee, Yijun Du, Jing Qi","doi":"10.1371/journal.ppat.1012622","DOIUrl":"10.1371/journal.ppat.1012622","url":null,"abstract":"<p><p>Non-POU domain-containing octamer-binding protein (NONO) is a multi-functional nuclear protein which belongs to the Drosophila behavior/human splicing (DBHS) protein family. NONO is known to regulate multiple important biological processes including host antiviral immune response. However, whether NONO can inhibit porcine reproductive and respiratory syndrome virus (PRRSV) replication is less well understood. In this study, we demonstrated that swine NONO (sNONO) inhibited PRRSV replication, via increasing expression of IFN-β, whereas NONO knockdown or knockout in PAM-KNU cells was more susceptible to PRRSV infection. As an IRF3 positive regulation factor, NONO promoted IFN-β expression by enhancing activation of IRF3. During PRRSV infection, NONO further up-regulated IRF3-mediated IFN-β expression by interacting with PRRSV N protein. Mechanistically, NONO functioned as a scaffold protein to detect PRRSV N protein and formed N-NONO-IRF3 complex in the nucleus. Interestingly, it was found that the NONO protein reversed the inhibitory effect of PRRSV N protein on type I IFN signaling pathway. Taken together, our study provides a novel mechanism for NONO to increase the IRF3-mediated IFN-β activation by interacting with the viral N protein to inhibit PRRSV infection.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 10","pages":"e1012622"},"PeriodicalIF":5.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478586","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}

{"title":"Do morphogenetic switching and intraspecies variation enhance virulence of Candida auris?","authors":"Trinh Phan-Canh, Karl Kuchler","doi":"10.1371/journal.ppat.1012559","DOIUrl":"10.1371/journal.ppat.1012559","url":null,"abstract":"<p><p>Intraspecies variations that affect pathogenicity and antifungal resistance traits pose a serious obstacle to efficient therapy of Candida auris infections. Recent reports indicate that mutations determine drug susceptibility and virulence. However, mutations alone cannot fully explain a bewildering variety of phenotypes in clinical isolates from known C. auris clades, suggesting an unprecedented complexity underlying virulence traits and antifungal resistance. Hence, we wish to discuss how phenotypic plasticity promotes morphogenetic switching and how that contributes to intraspecies variations in the human fungal pathogen C. auris. Further, we will also discuss how intraspecies variations and morphogenetic events can impact the progress in molecular mycology research that aims to find better treatments for C. auris infections. Finally, we will present our opinion as to the most relevant questions to be addressed when trying to better understand the pathophysiology of C. auris.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 10","pages":"e1012559"},"PeriodicalIF":5.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11478855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478574","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}

{"title":"Discovery, recognized antigenic structures, and evolution of cross-serotype broadly neutralizing antibodies from porcine B-cell repertoires against foot-and-mouth disease virus.","authors":"Fengjuan Li, Shanquan Wu, Lv Lv, Shulun Huang, Zelin Zhang, Zhaxi Zerang, Pinghua Li, Yimei Cao, Huifang Bao, Pu Sun, Xingwen Bai, Yong He, Yuanfang Fu, Hong Yuan, Xueqing Ma, Zhixun Zhao, Jing Zhang, Jian Wang, Tao Wang, Dong Li, Qiang Zhang, Jijun He, Zaixin Liu, Zengjun Lu, Dongsheng Lei, Kun Li","doi":"10.1371/journal.ppat.1012623","DOIUrl":"10.1371/journal.ppat.1012623","url":null,"abstract":"<p><p>It is a great challenge to isolate the broadly neutralizing antibodies (bnAbs) against foot-and-mouth disease virus (FMDV) due to its existence as seven distinct serotypes without cross-protection. Here, by vaccination of pig with FMDV serotypes O and A whole virus antigens, we obtained 10 bnAbs against serotypes O, A and/or Asia1 by dissecting 216 common clonotypes of two serotypes O and A specific porcine B-cell receptor (BCR) gene repertoires containing total 12720 B cell clones, indicating the induction of cross-serotype bnAbs after sequential vaccination with serotypes O and A antigens. The majority of porcine bnAbs (9/10) were derived from terminally differentiated B cells of different clonal lineages, which convergently targeted the conserved \"RGDL\" motif on structural protein VP1 of FMDV by mimicking receptor recognition to inhibit viral attachment to cells. Cryo-EM complex structures revealed that the other bnAb pOA-2 specifically targets a novel inter-pentamer antigen structure surrounding the viral three-fold axis, with a highly conserved determinant at residue 68 on VP2. This unique binding pattern enabled cross-serotype neutralization by destabilizing the viral particle. The evolutionary analysis of pOA-2 demonstrated its origin from an intermediate B-cell, emphasizing the crucial role of somatic hypermutations (SHMs) in balancing the breadth and potency of neutralization. However, excessive SHMs may deviate from the trajectory of broad neutralization. This study provides a strategy to uncover bnAbs against highly mutable pathogens and the cross-serotype antigenic structures to explore broadly protective FMDV vaccine.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 10","pages":"e1012623"},"PeriodicalIF":5.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11508087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478571","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}

{"title":"A master regulator of central carbon metabolism directly activates virulence gene expression in attaching and effacing pathogens.","authors":"Kabo R Wale, Nicky O'Boyle, Rebecca E McHugh, Ester Serrano, David R Mark, Gillian R Douce, James P R Connolly, Andrew J Roe","doi":"10.1371/journal.ppat.1012451","DOIUrl":"10.1371/journal.ppat.1012451","url":null,"abstract":"<p><p>The ability of the attaching and effacing pathogens enterohaemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium to overcome colonisation resistance is reliant on a type 3 secretion system used to intimately attach to the colonic epithelium. This crucial virulence factor is encoded on a pathogenicity island known as the Locus of Enterocyte Effacement (LEE) but its expression is regulated by several core-genome encoded transcription factors. Here, we unveil that the core transcription factor PdhR, traditionally known as a regulator of central metabolism in response to cellular pyruvate levels, is a key activator of the LEE. Through genetic and molecular analyses, we demonstrate that PdhR directly binds to a specific motif within the LEE master regulatory region, thus activating type 3 secretion directly and enhancing host cell adhesion. Deletion of pdhR in EHEC significantly impacted the transcription of hundreds of genes, with pathogenesis and protein secretion emerging as the most affected functional categories. Furthermore, in vivo studies using C. rodentium, a murine model for EHEC infection, revealed that PdhR is essential for effective host colonization and maximal LEE expression within the host. Our findings provide new insights into the complex regulatory networks governing bacterial pathogenesis. This research highlights the intricate relationship between virulence and metabolic processes in attaching and effacing pathogens, demonstrating how core transcriptional regulators can be co-opted to control virulence factor expression in tandem with the cell's essential metabolic circuitry.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 10","pages":"e1012451"},"PeriodicalIF":5.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11508082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478568","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}

{"title":"Host 5-HT affects Plasmodium transmission in mosquitoes via modulating mosquito mitochondrial homeostasis.","authors":"Li Gao, Benguang Zhang, Yuebiao Feng, Wenxu Yang, Shibo Zhang, Jingwen Wang","doi":"10.1371/journal.ppat.1012638","DOIUrl":"10.1371/journal.ppat.1012638","url":null,"abstract":"<p><p>Malaria parasites hijack the metabolism of their mammalian host during the blood-stage cycle. Anopheles mosquitoes depend on mammalian blood to lay eggs and to transmit malaria parasites. However, it remains understudied whether changes in host metabolism affect parasite transmission in mosquitoes. In this study, we discovered that Plasmodium infection significantly decreased the levels of the tryptophan metabolite, 5-hydroxytryptamine (5-HT), in both humans and mice. The reduction led to the decrease of 5-HT in mosquitoes. Oral supplementation of 5-HT to Anopheles stephensi enhanced its resistance to Plasmodium berghei infection by promoting the generation of mitochondrial reactive oxygen species. This effect was due to the accumulation of dysfunctional mitochondria caused by 5-HT-mediated inhibition of mitophagy. Elevating 5-HT levels in mouse serum significantly suppressed parasite infection in mosquitoes. In summary, our data highlight the critical role of metabolites in animal blood in determining the capacity of mosquitoes to control parasite infection.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 10","pages":"e1012638"},"PeriodicalIF":5.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11508672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478578","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}

{"title":"pK205R targets the proximal element of IFN-I signaling pathway to assist African swine fever virus to escape host innate immunity at the early stage of infection.","authors":"Zhao Huang, Cuiying Kong, WenBo Zhang, Jianyi You, Chenyang Gao, Jiangnan Yi, Zhanzhuo Mai, Xiongnan Chen, Pei Zhou, Lang Gong, Guihong Zhang, Heng Wang","doi":"10.1371/journal.ppat.1012613","DOIUrl":"10.1371/journal.ppat.1012613","url":null,"abstract":"<p><p>African swine fever virus (ASFV) is a nuclear cytoplasmic large DNA virus (NCLDV) that causes devastating hemorrhagic diseases in domestic pigs and wild boars, seriously threatening the development of the global pig industry. IFN-I plays an important role in the body's antiviral response. Similar to other DNA viruses, ASFV has evolved a variety of immune escape strategies to antagonize IFN-I signaling and maintain its proliferation. In this study, we showed that the ASFV early protein pK205R strongly inhibited interferon-stimulated genes (ISGs) as well as the promoter activity of IFN-stimulated regulatory elements (ISREs). Mechanistically, pK205R interacted with the intracellular domains of IFNAR1 and IFNAR2, thereby inhibiting the interaction of IFNAR1/2 with JAK1 and TYK2 and hindering the phosphorylation and nuclear translocation of STATs. Subsequently, we generated a recombinant strain of the ASFV-pK205R point mutation, ASFV-pK205R7PM. Notably, we detected higher levels of ISGs in porcine alveolar macrophages (PAMs) than in the parental strain during the early stages of ASFV-pK205R7PM infection. Moreover, ASFV-pK205R7PM attenuated the inhibitory effect on IFN-I signaling. In conclusion, we identified a new ASFV immunosuppressive protein that increases our understanding of ASFV immune escape mechanisms.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 10","pages":"e1012613"},"PeriodicalIF":5.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11508493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478583","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}

{"title":"Characterisation of the antibody-mediated selective pressure driving intra-host evolution of SARS-CoV-2 in prolonged infection.","authors":"Michael Schoefbaenker, Theresa Günther, Eva Ulla Lorentzen, Marie-Luise Romberg, Marc Tim Hennies, Rieke Neddermeyer, Marlin Maybrit Müller, Alexander Mellmann, Chiara Robin Bojarzyn, Georg Lenz, Matthias Stelljes, Eike Roman Hrincius, Richard Vollenberg, Stephan Ludwig, Phil-Robin Tepasse, Joachim Ewald Kühn","doi":"10.1371/journal.ppat.1012624","DOIUrl":"10.1371/journal.ppat.1012624","url":null,"abstract":"<p><p>Neutralising antibodies against the SARS-CoV-2 spike (S) protein are major determinants of protective immunity, though insufficient antibody responses may cause the emergence of escape mutants. We studied the humoral immune response causing intra-host evolution in a B-cell depleted, haemato-oncologic patient experiencing clinically severe, prolonged SARS-CoV-2 infection with a virus of lineage B.1.177.81. Following bamlanivimab treatment at an early stage of infection, the patient developed a bamlanivimab-resistant mutation, S:S494P. After five weeks of apparent genetic stability, the emergence of additional substitutions and deletions within the N-terminal domain (NTD) and the receptor binding domain (RBD) of S was observed. Notably, the composition and frequency of escape mutations changed in a short period with an unprecedented dynamic. The triple mutant S:Delta141-4 E484K S494P became dominant until virus elimination. Routine serology revealed no evidence of an antibody response in the patient. A detailed analysis of the variant-specific immune response by pseudotyped virus neutralisation test, surrogate virus neutralisation test, and immunoglobulin-capture enzyme immunoassay showed that the onset of an IgM-dominated antibody response coincided with the appearance of escape mutations. The formation of neutralising antibodies against S:Delta141-4 E484K S494P correlated with virus elimination. One year later, the patient experienced clinically mild re-infection with Omicron BA.1.18, which was treated with sotrovimab and resulted in an increase in Omicron-reactive antibodies. In conclusion, the onset of an IgM-dominated endogenous immune response in an immunocompromised patient coincided with the appearance of additional mutations in the NTD and RBD of S in a bamlanivimab-resistant virus. Although virus elimination was ultimately achieved, this humoral immune response escaped detection by routine diagnosis and created a situation temporarily favouring the rapid emergence of various antibody escape mutants with known epidemiological relevance.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 10","pages":"e1012624"},"PeriodicalIF":5.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11508484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478570","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}