PLoS Pathogens最新文献

{"title":"How post-translational modifications in pathogenic fungi inform pathogenesis and immune responses.","authors":"Satya Ranjan Sahu, Charles A Specht, Stuart M Levitz","doi":"10.1371/journal.ppat.1014162","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014162","url":null,"abstract":"","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014162"},"PeriodicalIF":4.9,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857533","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":"SPRY domains encode ubiquitin ligase specificity for ZAP and RIG-I.","authors":"Ibrahim Syed, Sheng Chen, David J Peeler, Paul F McKay, Marco A Briones-Orta, Jennifer A Bohn, Robin J Shattock, Daniel Gonçalves-Carneiro","doi":"10.1371/journal.ppat.1014195","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014195","url":null,"abstract":"<p><p>Innate immune sensors rely on ubiquitin ligases to calibrate antiviral responses, yet the rules governing substrate recognition by SPRY-containing ligases remain poorly defined. Here, we establish a large-scale structure-based screening pipeline using AlphaFold to systematically predict interactions between human nucleic acid sensors and SPRY-containing proteins. Our approach uncovered novel transient or degradation-sensitive interactions that are typically missed by proteomic methods, including a labile TRIM58-OAS1 complex. We show that SPRY domains dictate substrate specificity: TRIM25 preferentially engages ZAP, whereas Riplet favors RIG-I. Domain-swapping experiments demonstrated that SPRY domains are sufficient to reprogram ligase specificity and antiviral activity. Phylogenetic and structural analyses revealed that TRIM25 and Riplet evolved from a common ancestor but diverged in coiled-coil architecture and oligomeric state, while retaining conserved substrate preferences. Residue-level modeling identified hypervariable SPRY loops as critical determinants of recognition, a prediction validated by targeted mutagenesis of the TRIM25-ZAP interface. Finally, we show that distinct SPRY-containing ligases surveil self-amplifying RNA (saRNA) vaccines: Riplet-RIG-I primarily responds when RNA is delivered by lipofection, whereas TRIM25-ZAP is engaged upon lipid nanoparticle delivery, with functional consequences for vaccine expression. Together, these findings demonstrate that SPRY domains encode recognition logic for ubiquitin ligases, that AlphaFold enables discovery of otherwise hidden interactions and that these principles have direct implications for RNA-based therapeutics.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014195"},"PeriodicalIF":4.9,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857514","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":"Wolbachia-induced Cytoplasmic Incompatibility drives epigenetic and maternally-influenced post-embryonic defects.","authors":"Claire Perez, Jillian Porter, Brandt Warecki, William Sullivan","doi":"10.1371/journal.ppat.1014180","DOIUrl":"10.1371/journal.ppat.1014180","url":null,"abstract":"<p><p>A common form of Wolbachia-induced manipulation of host reproduction is Cytoplasmic Incompatibility (CI). In CI, Wolbachia modification of sperm results in pronounced defects in paternal chromosome condensation, replication, and segregation during the first mitotic division. Recent studies in D. simulans demonstrate that CI also induces independent and distinct later developmental defects resulting in high rates of mitotic errors during the mid-blastula transition and larval lethality. Here we show that in D. melanogaster, embryos derived from CI crosses experienced significant mitotic defects during gastrulation and increased larval lethality, both of which were eliminated in the progeny of Rescue crosses (both sexes infected). Examination of CI using females from 13 genetically distinct wild-type lines of the Drosophila Genetic Reference Panel (DGRP) revealed significant variation in the strength of the CI-induced lethality. Early embryonic pre-hatching and late larval lethal phases were uncorrelated, suggesting distinct factors influence the extent of the two lethal phases. Additionally, 3rd instar larvae and adults derived from D. melanogaster CI crosses exhibited locomotor defects that were also eliminated in Rescue crosses. These studies support a model in which Wolbachia effects on the sperm chromatin produce delayed developmental and locomotor defects, suggesting the involvement of epigenetic mechanisms. Support for this idea comes from our finding that levels of the heritable chromatin mark H3K27me1 are significantly elevated in CI-derived embryos. We conclude that the full measure of CI strength should take into account pre- and post-hatching lethality as well as locomotor defects. Together our findings suggest that the strength of these CI-induced phenotypes is governed at least in part by epigenetics and the maternal genetic background.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014180"},"PeriodicalIF":4.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13152123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845040","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":"An IL-1, IL-17, and IL-22 cytokine circuit controls vulvovaginal candidiasis independently of estrogen.","authors":"Bianca M Coleman, Melissa E Cook, Md Robin Khan, Amanda K Vogel, Anthony J Wells, Jian Miao, Shachi P Vyas, Tiffany C Taylor, Felix E Y Aggor, Nicole O Ponde, Ipsita Dey, Henry Zou, Eldin Jašarević, Brian M Peters, Sarah L Gaffen","doi":"10.1371/journal.ppat.1014202","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014202","url":null,"abstract":"<p><p>Vulvovaginal candidiasis (VVC) affects >75% of women, with considerable morbidity and high medical cost burden. While Type 17 cytokines (IL-17, IL-22) are critical for oral and dermal immunity to C. albicans, their role in VVC has been less clear. Th17 gene signatures are potently upregulated in VVC, yet impairment of individual Th17 components (IL-17A, IL-17R subunits, IL-22) does not worsen disease. Rather, estrogen activity is tightly linked to VVC, leading to a paradigm that hormonal pathways, rather than immune defense, dominate susceptibility. Here, we reveal a previously unappreciated role for IL-1/Type 17 in VVC that operates independently of estrogenic hormones. In contrast to mice lacking IL-17A, IL-17RA, IL-22, or IL-22R individually, mice lacking IL-17RA and IL-22RA1 together (Il17raIl22ra1-/-) exhibited high fungal loads and exacerbated tissue damage and inflammation during estrogen-induced VVC. In human vulvar epithelial cells, IL-17 and IL-22 drive synergistic signaling. IL-1R signaling but surprisingly not IL-23 was upstream of this response. Il17raIl22ra1-/- mice expressed high IL-1β yet did not control disease, indicating that IL-1 is upstream but not downstream of Type 17 responses. Unexpectedly, Type 17-dependent control occurred in the absence of exogenous estrogen administration and persisted even when estrus was prevented by progesterone treatment. Collectively, these data indicate that susceptibility to VVC is driven not only by estrogen sensitization but through combinatorial loss of IL-17 and IL-22.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014202"},"PeriodicalIF":4.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844690","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":"Weak selection and stochastic processes limit the emergence of antigenic variants during household transmission of influenza A viruses.","authors":"Hunter J Ries, Joseph Lalli, Kelsey R Florek, Shari Barlow, Maureen Goss, Richard Griesser, Tonya Danz, Amra Uzicanin, Jonathan Temte, Thomas C Friedrich","doi":"10.1371/journal.ppat.1013689","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013689","url":null,"abstract":"<p><p>Influenza viruses undergo antigenic drift, the gradual accumulation of mutations that cause antigenic changes in the viral surface proteins hemagglutinin (HA) and neuraminidase (NA). Although selection for antigenic variants is detectable on the global scale, the processes by which antigenic variants are generated and selected in individual hosts remain unclear. It has been hypothesized that selection for antigenic variants may occur during the establishment of a new infection, rather than over time in a single host. Here, we leveraged a large household cohort study to assess whether selection was detectable between acutely infected hosts. We investigated influenza A virus evolution using specimens from 384 children and household contacts with RT-PCR-confirmed influenza A infection, representing infections with A(H1N1)pdm09 and A(H3N2) viruses from 2017-19. In agreement with prior studies, we found that acute infections involved weak purifying selection across the viral genome. In addition, we identified 40 transmission events occurring in 31 households. During transmission, evolution between hosts was characterized by tight transmission bottlenecks and weak purifying selection. We found variability in the strength and direction of selection on antigenic regions of HA, but no clear evidence for selection of antigenic variants during transmission. Together, our results indicate that stochastic processes and weak natural selection dominate most acute influenza A virus infections and transmission events, and that selection of antigenic variants during transmission between acutely infected hosts is likely to be exceedingly rare.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1013689"},"PeriodicalIF":4.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844969","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":"Tracking fungal pathogens on cancer: Oncomicrobes or opportunistic bystanders?","authors":"Rosana Alves, Wouter Van Genechten, Patrick Van Dijck","doi":"10.1371/journal.ppat.1014179","DOIUrl":"10.1371/journal.ppat.1014179","url":null,"abstract":"","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014179"},"PeriodicalIF":4.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13152125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845023","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":"Globodera pallida virulence on major potato resistance has a common genetic basis across Western Europe.","authors":"Arno S Schaveling, Leidy van Rijt, Yoonseon Do, Nike Soffree, Daan Langendoen, Hilde Room, André Machado Bertran, Margien Raven, Sebastiaan P van Kessel, Evelyn Y J van Heese, Stefan J S van de Ruitenbeek, Casper C van Schaik, Sebastian Kiewnick, Geert Smant, Mark G Sterken","doi":"10.1371/journal.ppat.1014201","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014201","url":null,"abstract":"<p><p>The potato cyst nematode Globodera pallida poses a major threat to potato production in Western Europe. Current management strategies largely depend on the use of potato varieties carrying the genetic resistance GpaVvrn. However, reports from multiple West-European countries indicate a steady rise in virulence against GpaVvrn-containing potato varieties, raising serious concerns about G. pallida control. Although recent studies have resolved the genetic basis of virulence in two Dutch G. pallida populations, it remains unclear how conserved this genetic adaptation is in populations from different regions. To investigate this, we first selected eight Dutch G. pallida populations on the GpaVvrn-containing potato variety Seresta and confirmed a previously identified virulence locus. Second, by analysing the allele frequencies of four virulence-associated SNPs in Dutch, British, and French GpaVvrn-selected G. pallida populations, we found that the same allele is consistently selected by GpaVvrn across Western Europe. Third, we analysed the propagation of eight G. pallida populations on 26 GpaVvrn-containing potato varieties and showed that a population's allele frequency of a single SNP (T173N) accurately reflects its reproduction on GpaVvrn. Fourth, we developed an allele-specific quantitative PCR (AS-qPCR) assay to determine a population's alternative allele frequency (AAF) of T173N and showed that AS-qPCR-based AAFs reliably indicate virulence levels on GpaVvrn in Dutch and German G. pallida populations. Together, these findings suggest that a common allele is consistently selected by GpaVvrn in populations from different regions across Western Europe. The AS-qPCR assay developed in this study provides a practical tool to estimate G. pallida virulence on GpaVvrn in the field, enabling field-tailored and sustainable resistance management strategies for farmers.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014201"},"PeriodicalIF":4.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844938","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 stage-specific regulation and role of root-knot nematode SWEET genes.","authors":"M Willow H Maxwell, Bharat Rohilla, Jasper Chippendale, Chris A Bell","doi":"10.1371/journal.ppat.1014161","DOIUrl":"10.1371/journal.ppat.1014161","url":null,"abstract":"<p><p>The root-knot nematode Meloidogyne incognita is a globally significant plant parasite that causes substantial crop losses. While pre-parasitic juveniles rely on innate energy reserves, later life stages acquire nutrients from host plants through specialized feeding structures. SWEET (Sugars Will Eventually be Exported Transporter) genes exhibit a conserved sugar transporting ability across all kingdoms of life, yet their function in plant-parasitic nematodes remains underexplored. Here, we functionally characterise the SWEET gene family in M. incognita, revealing their critical and stage-specific roles in nematode development and parasitism. We demonstrate that Mi-SWEETs segregate into two functional groups: those that facilitate mobility and invasion in motile juveniles (Mi-SWEET2, 4) and those support nutrient uptake during feeding (Mi-SWEET3, 5, 7). Although temporally distinct, all SWEET genes localise to the intestine, suggesting a conserved role in mediating sugar flux. Knockdown of Mi-SWEET2 and Mi-SWEET4 reduced root invasion, while silencing Mi-SWEET3, 5, and 7 impaired post-invasion growth, highlighting the varied roles of this large gene family across different life stages. Yeast complementation assays revealed distinct substrate preferences among Mi-SWEETs, aligning with the metabolic needs of different life stages. The transcription factor HBL1, a key regulator of nematode dietary responses, was found to control the expression of Mi-SWEET3 and is itself regulated through interaction with the post-transcriptional regulatory microRNA let-7. Our findings provide new insights into the metabolic adaptations and energy utilisation of plant-parasitic nematodes and outline a microRNA - transcription factor - target gene regulatory network. These findings have broader relevance given the fundamental importance of the regulation of resource transportation in plant-pathogen interactions.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014161"},"PeriodicalIF":4.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844962","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":"Human herpesvirus 7 integrates into host telomeres via its telomeric repeat arrays.","authors":"Yingnan Cheng, Joilson Xavier, Dusan Kunec, Jana Reich, Christiana Victoria Cismaru, Dilan Gün Serdar, Thomas Höfler, Benedikt B Kaufer","doi":"10.1371/journal.ppat.1014189","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014189","url":null,"abstract":"<p><p>Human herpesvirus 7 (HHV-7) is a ubiquitous betaherpesvirus and a causative agent of roseola infantum. HHV-7 harbors telomeric repeat arrays (TMR) identical to human telomeres at the ends of its genome. While similar repeats contribute to human herpesvirus 6 (HHV-6) integration into host telomeres, HHV-7 integration and the role of the TMR remained elusive. Using fluorescence in situ hybridization and nanopore sequencing, we demonstrate that HHV-7 efficiently integrates into host telomeres in persistently infected cells. To determine the role of the TMR in the virus life cycle, we generated the first HHV-7 reverse genetic system and mutants lacking the TMR. These mutants revealed that the TMR are dispensable for HHV-7 replication, but play a crucial role in the integration process and genome maintenance in persistently infected cells. This study provides a reverse genetic system for HHV-7, and offers important insights into the biology of this ubiquitous human pathogen.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014189"},"PeriodicalIF":4.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844859","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":"Coronavirus M protein disperses the trans-Golgi network and inhibits anterograde protein trafficking in the secretory pathway.","authors":"Taylor M Caddell, Rory P Mulloy, Jennifer A Corcoran, Eric S Pringle, Craig McCormick","doi":"10.1371/journal.ppat.1014117","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014117","url":null,"abstract":"<p><p>Coronaviruses (CoVs) encode a variety of transmembrane proteins that are translated and processed at the endoplasmic reticulum (ER). Three host ER resident transmembrane proteins, activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1), and PKR-like endoplasmic reticulum kinase (PERK), sense the accumulation of unfolded proteins in the ER and initiate the unfolded protein response (UPR) to maintain ER proteostasis. We observed that SARS-CoV-2 Spike broadly activated all three arms of the UPR, whereas the Membrane (M) protein selectively inhibited ATF6. ATF6 has a unique activation mechanism whereby ER stress triggers translocation to the Golgi where ATF6 is processed by resident proteases to release the ATF6-N transcription factor. We observed that M inhibited the stress-induced production of ATF6-N, suggesting that ATF6 failed to engage with Golgi proteases for processing. M also inhibited sterol regulatory element binding protein-2 (SREBP2)-mediated activation of sterol responses and stimulator of interferon response cGAMP interactor 1 (STING)-mediated activation of interferon responses, both of which are activated in the ER and require translocation to the Golgi for interactions that yield transcriptional responses. We observed that M accumulated in the cis-Golgi, and triggered dispersal of the trans-Golgi network (TGN). Using a cargo sorting assay, we determined that ER-to-Golgi cargo trafficking was intact in the presence of M, but cargo accumulated with M in the cis-Golgi and did not proceed further in the secretory pathway. We also observed aberrant cholesterol accumulation at the cis-Golgi with M, consistent with our observation of M association with detergent resistant membranes. Together, these data suggest that CoV M proteins interfere with Golgi architecture and trafficking. Because CoV egress does not require the canonical secretory pathway, this mechanism could allow the virus to selectively interfere with host responses to infection without impeding egress of nascent virions.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014117"},"PeriodicalIF":4.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844935","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}