Journal of General Virology最新文献

{"title":"Identification and functional validation of AU-rich and stem-loop structures as key determinants of recombination hotspots in the PRRSV NSP9 gene.","authors":"Xindong Wang, Yanli Pang, Yiting Chen, QingRong Mo, Kang Zhang, Guochang Chen, Zhiying Su, Keyi Liu, Tongwei Ren, Yifeng Qin, Kang Ouyang, Yeshi Yin, Ying Chen, Weijian Huang, Zuzhang Wei","doi":"10.1099/jgv.0.002289","DOIUrl":"10.1099/jgv.0.002289","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome virus (PRRSV) employs RNA recombination to generate phenotypic variants that evade host immunity, with recombination hotspots frequently observed in the NSP9 gene of field strains. This study investigates the structural determinants of recombination hotspots in the NSP9 gene by integrating bioinformatics analyses and <i>in vitro</i> and <i>in vivo</i> co-infection experiments. We identified three high-frequency recombination hotspots (7492-7624 nt, 7887-7940 nt and 9009-9464 nt) characterized by AU-rich sequences and stem-loop structures. Notably, these hotspot profiles were conserved between field-derived strains and <i>in vitro</i> co-infection models, supporting the use of experimental systems to highlight candidate recombination-prone contexts. To assess the functional role of RNA motifs, synonymous mutations disrupting AU-rich regions or secondary structures were engineered into the 7887-7940 nt hotspot. These mutations significantly reduced recombination rates, underscoring the contribution of local nucleotide composition and structural features to recombination dynamics. Collectively, our findings define sequence/structure contexts that shape PRRSV recombination signatures and provide a mechanistic framework that may inform efforts to improve the genetic stability of live vaccine candidates by reducing recombination propensity while acknowledging that validation in porcine target cells and/or <i>in vivo</i> models is required.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of cell lines persistently infected with infectious pancreatic necrosis virus.","authors":"Lise Chaumont, Mathilde Peruzzi, François Huetz, Claudine Raffy, Jérôme Le Hir, Jules Minke, Pierre Boudinot, Bertrand Collet","doi":"10.1099/jgv.0.002283","DOIUrl":"10.1099/jgv.0.002283","url":null,"abstract":"<p><p>Infectious pancreatic necrosis virus (IPNV) is a major pathogen of salmonids that is capable of establishing persistent infections, yet the cellular mechanisms underlying viral persistence remain poorly understood. In this study, we characterized two Chinook salmon embryo-derived cell lines - a wild-type and a Protein Kinase R (PKR)-deficient cell line - which were found to be persistently infected with IPNV. Both cell lines displayed hallmark features of viral persistence, including sustained cell growth without cytopathic effect, continuous production of infectious virus over successive passages and resistance to superinfection by homologous IPNV strains and susceptibility to heterologous viruses. Longitudinal analyses over 40 weekly passages revealed pronounced oscillations in extracellular infectious titres, which partially correlated with fluctuations in intracellular viral RNA levels. Despite these variations in viral replication, persistent infection did not trigger a robust type I interferon response, and basal expression of key interferon-stimulated genes was dampened. Notably, the absence of PKR did not alter viral persistence dynamics, indicating that PKR is not a regulator of this process. Taken together, these findings suggest that persistent IPNV employs immune evasion strategies to suppress host innate immune signalling while maintaining low-level replication.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13278376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ICTV Virus Taxonomy Profile: <i>Rhabdoviridae</i> 2026.","authors":"Peter J Walker, Nicolas Bejerman, Kim R Blasdell, Humberto Debat, Ralf G Dietzgen, Anthony R Fooks, Juliana Freitas-Astúa, Kyle Garver, Hideki Kondo, Pedro Luis Ramos-González, Mang Shi, Robert B Tesh, Noël Tordo, Nikos Vasilakis, Anna E Whitfield","doi":"10.1099/jgv.0.002255","DOIUrl":"10.1099/jgv.0.002255","url":null,"abstract":"<p><p>The family <i>Rhabdoviridae</i> comprises viruses with unsegmented, bi-segmented or tri-segmented negative-sense (-) RNA genomes of 10-16 kb. Virions are typically enveloped, with bullet-shaped or bacilliform morphology, but can also be non-enveloped filaments. Rhabdoviruses infect plants or animals, including vertebrates or invertebrates such as arthropods, which can serve as single hosts or act as biological vectors for transmission to animals or plants. Rhabdoviruses include important pathogens of humans, livestock, fish or agricultural crops. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family <i>Rhabdoviridae</i>, which is available at ictv.global/report/rhabdoviridae.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Historical and contemporary chronic wasting disease prions from the western United States demonstrate similar strain properties.","authors":"Katie Williams, Chase Baune, Daniel Shoup, Tina Thomas, James F Striebel, Suzette A Priola, Karen A Griffin, Michael W Miller, Kent Barbian, Kaitlyn Wagner, Mark D Zabel, Brent Race","doi":"10.1099/jgv.0.002265","DOIUrl":"10.1099/jgv.0.002265","url":null,"abstract":"<p><p>Chronic wasting disease (CWD) is a uniformly fatal prion disease of cervids including deer, elk, reindeer and moose. CWD has been detected in cervids of North America (NA), South Korea and Scandinavia. CWD in NA continues to increase in prevalence in multiple locations and is relatively widespread in both wild and captive cervid populations. Consequently, the potential for CWD cross-species exposure to humans or animals that consume or cohabitate with infected cervids continues to increase. Fortunately, CWD infection in humans has not been detected to date, and both laboratory models and epidemiological studies suggest that a strong species barrier exists between cervids and humans. In recent years, several different strains of CWD have been identified and characterized. Unfortunately, new strains of CWD prions may harbour different abilities to cross species barriers, presenting a situation where the risks to humans and animals may also vary. To gain a better understanding of the variation in CWD strains circulating in NA, we performed strain characterization of ten CWD isolates obtained over the past 4-30 years from white-tailed deer, mule deer and elk representing infections from several geographical regions in the western United States. Our results showed that all the cervid isolates we tested had similar prion strain characteristics, suggesting that the CWD prions circulating in the western United States have remained very similar across multiple locations and stable over time.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A stable subgenomic reporter coronavirus enables transcriptional profiling of bystander cells.","authors":"Ciaran Gilbride, Joe Hemsley-Taylor, Catarina Nunes, Rebecca Penn, James Boot, Nima Pieris, Rupa Tripathy, Ziyi Yang, Matthew Hutchinson, Olivia K Platt, Rachel Ulferts, Richard Mitter, Molly Strom, Nuno B Santos, David L V Bauer, Harriet V Mears","doi":"10.1099/jgv.0.002282","DOIUrl":"10.1099/jgv.0.002282","url":null,"abstract":"<p><p>Insertion of fluorescent reporter genes into viral genomes is a powerful tool for monitoring infection. In coronaviruses, this is commonly achieved by replacing accessory ORFs, thereby deleting endogenous gene functions. An alternative strategy is to manipulate viral RNA synthesis by inserting copies of the viral transcription regulatory sequence (TRS), which drives the transcription of viral subgenomic RNAs. However, coronavirus transcription is tightly regulated, and these modifications frequently disrupt native subgenomic RNA synthesis and attenuate viral growth. Here, we describe a reporter coronavirus that overcomes these limitations. Using human coronavirus (HCoV)-OC43 as a model system, we inserted an mNeonGreen reporter between the Spike and ORF5 coding regions, engineering the TRS and surrounding sequence to minimize off-target effects to transcription. This virus is genetically stable, with WT growth kinetics and unaltered subgenomic RNA transcriptional ratios. We developed a flexible reverse genetics system, which allows rapid cloning and virus recovery, supported by optimized HCoV-OC43 culture conditions for high-titre stock generation, and validated analytical reagents. Our reporter virus enabled sensitive detection and isolation of infected cells, facilitating transcriptomic analyses that distinguish host responses in infected and bystander populations based on active viral translation. We found that transcriptional responses to infection of A549 human lung epithelial cells were predominantly inflammatory, rather than interferon-mediated, and that bystander cells upregulated pathways associated with cytokine response signalling and cell-cell contact sensing. Together, these tools expand the experimental utility of HCoV-OC43, an important seasonal respiratory pathogen and low-containment model for betacoronavirus biology.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental samples, a sensitive and practical alternative to individual bird sampling in the surveillance of H9N2 vaccinated turkey flocks.","authors":"Leonard Kalvelage, Maximillian Casteel, Maria Hartmann, Timm C Harder, Lothar Kreienbrock","doi":"10.1099/jgv.0.002279","DOIUrl":"10.1099/jgv.0.002279","url":null,"abstract":"<p><p>Surveillance for influenza A virus infections in vaccinated poultry flocks remains challenging due to animal welfare, logistical and financial constraints, particularly under current EU regulations governing high pathogenicity avian influenza (HPAI) vaccination. In this field study, we evaluated two environmental sampling (ES) methods - bedding boot swabs and drinker wipes - as alternatives to legally mandated individual bird testing, which involved monthly swabbing of 60 healthy birds (active surveillance, AS) and weekly swabbing of dead or sick birds (passive surveillance, PS). A total of 56 turkey flocks from 23 holdings in Lower Saxony, Germany, were monitored throughout the fattening period following single H9N2 vaccination at hatch. Semiquantitative reverse transcription polymerase chain reaction (RT-qPCR) revealed that, despite vaccination, H9N2 virus incursions occurred at least once in 76.8% (43/56) of flocks during the subsequent fattening period. Influenza A virus detection rate on the basis of individual samples was significantly higher by ES (24.1%) than through AS (10.65%; <i>P</i><0.0001) or PS (15.6%, <i>P</i>=0.001). Overall, ES demonstrated superior performance in identifying 42/43 infected flocks (99.67%) compared with 30/43 (69.97%) by AS and 38/43 (88.37%) by PS. Heatmap and event-time analyses confirmed that ES reliably identified infection events very early and remained positive longer after initial detection. Non-invasive, animal-friendly ES was easy to implement and well accepted by farmers. Costs for ES surveillance were reduced by 73.5% compared to AS and PS. ES was found to be a sensitive, cost-effective and very practical alternative to conventional surveillance in influenza-vaccinated poultry, with direct relevance for future surveillance strategies in HPAI vaccination programmes.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular surveillance and predictive risk modelling of avian influenza virus in wild birds in Egypt.","authors":"Nehal M Nabil, Maram M Tawakol, Naglaa Hagag, Samah Eid, Liam Brierley, Mahmoud M Naguib","doi":"10.1099/jgv.0.002278","DOIUrl":"10.1099/jgv.0.002278","url":null,"abstract":"<p><p>Avian influenza viruses (AIVs) continue to circulate and pose a persistent threat to animal and public health in Egypt, a country located along major migratory birds' flyways that enable repeated viral incursions. In this study, a total of 1,087 wild birds representing 19 species were sampled to assess the role of migratory wild birds in virus introduction and spread. Six species were found positive for AIV, with Eurasian teal showing the highest prevalence (12.3%). The H5 subtype was found predominant, representing 70.3% of positive cases, whereas H9 was detected in 9.9% of positive cases. Moreover, coinfections with H5/H9 were observed in Eurasian teal, Common moorhen and Northern pintail, suggesting opportunities for cocirculation among migratory species. To predict areas at high risk of AIV detection, these findings were integrated with additional publicly available geolocated AIV sampling records and a spatial machine learning (ML) model was trained. The model demonstrated moderate predictive performance (Area Under Curve =0.608; F1=0.596) and highlighted relative humidity, temperature and proximity to wetlands as primary predictors of AIV detection. In addition, risk projections for early winter underscore several areas including the Nile Delta, Nile River corridor, southern wetlands near Lake Nasser, the south-eastern Red Sea coast and the north-western Siwa region as areas of high risk of AIV detection. The findings of this study demonstrate the role of migratory wild birds in the spread and introduction of AIV into Egypt, particularly H5, and provide an ML-based model to predict areas of high risk of virus detection in Egypt, which could in turn strengthen early detection and guide mitigation strategies.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatitis B virus X protein induces E6-associated protein-mediated proteasomal degradation of p53 phosphorylated at Ser-15.","authors":"Jiwoo Han, Yerin Kwon, Ji-Min Park, Kyung Lib Jang","doi":"10.1099/jgv.0.002291","DOIUrl":"10.1099/jgv.0.002291","url":null,"abstract":"<p><p>The hepatitis B virus (HBV) X protein (HBx) activates the ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 (Chk2) pathway, leading to phosphorylation of p53 at multiple sites including Ser-15. This phosphorylation largely contributes to p53 accumulation by preventing its degradation via MDM2. This study further shows that HBx facilitates E6-associated protein (E6AP)-mediated proteasomal degradation of p53 during HBV replication. In the presence of HBx, E6AP expression induced p53 ubiquitination, reduced its stability and decreased p53 levels, whereas E6AP knockdown elevated p53 levels. The critical role of E3 ligase activity in E6AP was confirmed using the E6AP (C833A) mutant, the homologous to the E6-AP Carboxyl Terminus (HECT)-type ubiquitin E3 ligase inhibitor Heclin and the proteasome inhibitor MG132. E6AP-mediated p53 degradation was severely impaired in the presence of the ATM inhibitor KU-55933, indicating that HBx-induced p53 phosphorylation plays a critical role in this process. Additionally, E6AP could target p53 phosphorylated by DNA-damaging agents like etoposide in the absence of HBx. HBx also strengthened the interaction between phosphorylated p53 and E6AP, suggesting an additional mechanism that enhances E6AP-mediated ubiquitination of phosphorylated p53. Ser-15 phosphorylation was pivotal, as E6AP could degrade p53 S15D (phosphomimetic mutant) but failed to act on p53 S15A (a non-phosphorylatable mutant). These findings suggest that HBx-induced p53 phosphorylation enhances E6AP-mediated degradation while concurrently inhibiting MDM2-mediated pathways, thereby fine-tuning p53 levels to support cell survival, viral replication and potentially carcinogenesis during HBV infection in human hepatocytes.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13326589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signal peptide cleavage and ectodomain regions of GP2 are required for PRRSV infection.","authors":"Derek Pinto, Raymond R R Rowland, Alberto Brandariz-Nuñez","doi":"10.1099/jgv.0.002287","DOIUrl":"10.1099/jgv.0.002287","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome virus (PRRSV) is the most economically important pathogen of swine, yet the molecular mechanisms governing its entry into host cells remain incompletely understood. The minor envelope glycoprotein GP2, together with GP3 and GP4, forms an essential complex that engages the entry receptor CD163; however, the specific GP2 regions required for receptor association have not been fully defined experimentally. Here, we investigated GP2 processing, intracellular trafficking and interactions with viral glycoproteins and CD163. We demonstrate that the GP2 signal peptide (SP) is cleaved in both transfected and infected cells and is necessary and sufficient for ER localization. Removal of the SP disrupted GP2 maturation, impaired interactions with GP3, GP4 and GP5, and significantly reduced viral infectivity in infectious clone assays. Deletion of the SP also abolished GP2-CD163 association, indicating that proper SP-dependent processing is required for receptor engagement. Using co-immunoprecipitation and colocalization analyses, we identified two highly conserved regions within the GP2 ectodomain that associate with CD163. Deletion of either region completely eliminated PRRSV infection. Together, these findings define the structural determinants within GP2 required for association with CD163 and advance our understanding of the early steps of PRRSV entry.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13278558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NAD⁺ metabolism at the host-virus interface.","authors":"Prince Jhandai, Kishore Vaddadi, Lin Liu","doi":"10.1099/jgv.0.002285","DOIUrl":"10.1099/jgv.0.002285","url":null,"abstract":"<p><p>Nicotinamide adenine dinucleotide (NAD⁺) is one of the most important metabolic coenzymes that not only drives redox reactions and energy production but also acts as a critical substrate for several enzymes involved in immune signalling, DNA repair and epigenetic regulation. Viral infections are known as potent modulators of NAD⁺ metabolism, with pathogens such as SARS-CoV-2, influenza A virus, Zika virus, herpes simplex virus and human immunodeficiency virus altering NAD⁺ biosynthesis and consumption to benefit their persistence and replication. In this review, we summarize the current understanding of NAD⁺ metabolism and its regulatory enzymes: sirtuins, poly (ADP-ribose) polymerases and CD38/CD157. We then discuss the interplay between NAD⁺ homeostasis and virus infection. Understanding how diverse viruses manipulate NAD⁺ metabolism could lead to broad-spectrum antiviral strategies grounded in metabolic resilience.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13292451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}