Journal of Virology最新文献

{"title":"Sources and sinks of influenza A virus genomic diversity in swine from 2009 to 2022 in the United States.","authors":"Garrett M Janzen, Blake T Inderski, Jennifer Chang, Zebulun W Arendsee, Alicia Janas-Martindale, Mia Kim Torchetti, Amy L Baker, Tavis K Anderson","doi":"10.1128/jvi.00541-25","DOIUrl":"10.1128/jvi.00541-25","url":null,"abstract":"<p><p>Influenza A virus (IAV) in swine in the U.S. is surveilled to monitor genetic evolution to inform intervention efforts and aid pandemic preparedness. We describe data from the U.S. Department of Agriculture National Surveillance Plan for Influenza A Virus in Pigs from 2009 to 2022. Clinical respiratory cases were subtyped, followed by sequencing of hemagglutinin (HA) and neuraminidase (NA), and a subset of viruses was whole genome sequenced. Phylogenetic analysis identified geographic and temporal IAV reassortment hotspots. Regions acting as IAV genomic diversity sources or sinks were quantified, and dissemination was qualified and modeled. The dominant IAV clades were H1N2 (1B.2.1), H3N2 (1990.4.a), and H1N1 (H1-1A.3.3.3-c3). Internal genes were classified as triple-reassortant (T) or pandemic 2009 (P), and three genome constellations represented 73.5% of detections across the last 2 years. In some years, the distribution of IAV diversity was so narrow that it presented a statistical signal associated with local adaptation. We also demonstrated that the source of most IAV genomic diversity was in Midwest states (IL, MO, IA), and while this was correlated with swine inventory, the emergence and persistence of diversity were tied to swine transport across the U.S. The continued regional detection of unique HA, NA, and genome constellations provides support for targeted interventions to improve animal health and enhance pandemic preparedness.IMPORTANCEVariation in the genetic diversity of influenza A virus (IAV) in swine through time and between regions impacts control efforts. This study quantified the genomic diversity of swine IAV collected from 2009 to 2022 at regional and national levels and modeled sources and sinks of that diversity. Seasonal patterns of IAV transmission were observed, and some locations contributed disproportionately to the emergence of genomic diversity. Minor groups of viruses had the potential to disseminate across the U.S. with animal movement. The identification of these patterns demonstrates the importance of a robust surveillance system to inform vaccine updates that reflect regional patterns of genetic diversity. We show how preemptive interventions in swine IAV diversity hubs could reduce reassortment and the emergence of novel genomic diversity, and how these efforts are likely to reduce the transmission of IAV within swine and between swine and humans.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":"99 9","pages":"e0054125"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A versatile H5N1-VSV platform for safe influenza virus research applications.","authors":"Boopathi Sownthirarajan, Maya Mason, Gayathri Loganathan, Senthamizharasi Manivasagam, Rohit K Jangra, Gene S Tan, Daniel R Perez, Balaji Manicassamy","doi":"10.1128/jvi.00975-25","DOIUrl":"10.1128/jvi.00975-25","url":null,"abstract":"<p><p>The H5N1 strain of influenza A virus (IAV) continues to cause severe infections in a range of avian and mammalian species, including sporadic but concerning cases in humans. There is growing concern that circulating H5N1 strains could lead to widespread human outbreaks. Research with highly pathogenic H5N1 viruses is restricted to Biosafety Level 3 (BSL-3) laboratories. Vesicular stomatitis virus (VSV)-based vaccine vectors expressing heterologous viral proteins from Ebola, SARS-CoV-2, Lassa virus, etc., have previously been shown to be safe and effective in animal models and human clinical trials. Here, we report the development of a recombinant VSV expressing the hemagglutinin (HA) and neuraminidase (NA) genes of H5N1 IAV (H5N1-VSV), which serves as a versatile platform to study various aspects of H5N1 IAV biology. H5N1-VSV replicated robustly to titers comparable to those of the full H5N1 virus in multiple cell lines. In mice, H5N1-VSV vaccination was safe, elicited strong immunity, and conferred protection against a circulating H5N1 strain. Notably, we found that polymorphisms in antigenic site Sa of circulating strains emerged under immune selection pressure in cattle, resembling the evolution of pandemic IAV in humans. These findings suggest that H5N1-VSV can serve as a safe, adaptable platform for influenza research.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0097525"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatitis C virus NS3/4A protease cleaves SPG20, a key regulator of lipid droplet turnover, to promote lipid droplet formation.","authors":"Chieko Matsui, Putu Yuliandari, Lin Deng, Takayuki Abe, Ikuo Shoji","doi":"10.1128/jvi.00890-25","DOIUrl":"https://doi.org/10.1128/jvi.00890-25","url":null,"abstract":"<p><p>Hepatitis C virus (HCV) assembles in close proximity to lipid droplets (LDs), which play important roles in HCV RNA replication. HCV infection often causes the accumulation of large LDs in hepatocytes. However, the molecular mechanism underlying HCV-induced large LD formation is poorly understood. It has been reported that the SPG20/Spartin protein associates with the LD surface and plays a crucial role in LD turnover by recruiting the ubiquitin ligase Itch to promote the ubiquitin-dependent degradation of adipophilin (ADRP), which protects LDs from lipase-mediated degradation. To elucidate the mechanism underlying HCV-induced large LD formation, we investigated the SPG20 protein's role in LD formation in HCV J6/JFH1-infected Huh-7.5 cells. Immunoblot analysis revealed that HCV infection promoted SPG20 protein cleavage. Transfection of increasing amounts of NS3/4A, but not the inactive NS3/4A mutant, resulted in SPG20 cleavage, implicating the NS3/4A protease in this cleavage. Site-directed mutagenesis suggested that the NS3/4A protease cleaves SPG20 at Cys⁵⁰⁴ and Cys⁵⁶². The SPG20 protein was co-immunoprecipitated with the LD-attached protein TIP47. Increasing amounts of NS3/4A protease, but not inactive NS3/4A, decreased the co-precipitation of SPG20 with TIP47. The siRNA-mediated knockdown of Itch in Huh-7.5 cells restored ADRP levels, suggesting that Itch mediates ubiquitylation-dependent ADRP degradation. Immunofluorescence staining of HCV-infected cells revealed that ADRP was localized mainly around LDs in HCV-infected cells, whereas cytosolic ADRP was decreased. We propose that the HCV NS3/4A protease specifically cleaves SPG20 and inhibits Itch-mediated ubiquitin-dependent degradation of LD-associated ADRP, thereby promoting the formation of large LDs.IMPORTANCEHCV infection often promotes the formation of large LDs in HCV-infected cells. However, the molecular mechanism underlying large LD formation is poorly understood. LD turnover is regulated by SPG20, Itch E3 ligase, and ADRP. To elucidate the mechanism underlying the formation of large LDs induced by HCV infection, we investigated the roles of SPG20, Itch, and ADRP in large LD formation. The HCV NS3/4A protease specifically cleaves SPG20 and disrupts Itch recruitment to LD-associated ADRP. Therefore, LD-associated ADRP can escape and protects LDs from lipase-mediated degradation, thereby promoting LD growth. We propose that HCV NS3/4A protease-mediated cleavage of SPG20 contributes to a previously uncharacterized mechanism underlying the formation of large LDs in HCV-infected cells. These findings may lead to a better understanding of how the virus forms large LDs in infected cells.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0089025"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryo-EM structure of the Seneca Valley virus A-particle and related structural states.","authors":"Rosheny Kumaran, Nadishka Jayawardena, Kuan-Lin Chen, Alice-Roza Eruera, James Hodgkinson-Bean, Laura N Burga, Matthias Wolf, Mihnea Bostina","doi":"10.1128/jvi.00744-25","DOIUrl":"10.1128/jvi.00744-25","url":null,"abstract":"<p><p>Picornavirus cell entry requires a series of capsid protein conformational changes leading to genome uncoating. For enteroviruses, receptor binding triggers the transition from a full (F) capsid to an altered (A) particle before releasing its genome and finally converting it into an empty (E) particle. In contrast, non-enteroviruses, such as Aphthovirus, Cardiovirus, or Seneca Valley virus, release their genomes by dissociating the capsid into pentamers. While the existence of a transient A-particle for non-enteroviruses was previously speculated, it has never been directly observed using structural methods. Seneca Valley virus (SVV) is an oncolytic picornavirus that selectively targets cancer cells by recognizing Tumor endothelial marker 8 (TEM8) as the host receptor. SVV disassembles into pentamers at acidic pH, suggesting that the acidic environment of the endosome could cause capsid disassembly. We used cryo-electron microscopy to investigate SVV under acidic conditions and in complex with TEM8 at physiological pH, identifying multiple uncoating intermediates. These include an altered-particle, an empty-rotated particle (E^R), and a series of open particles expelling the coiled genome. The A-particle is expanded, displays reduced interactions between capsid proteins, a reorganized genome, and has a poorly resolved VP1 N-terminus, VP2 N-terminus, and VP4. The E^R particle has rotated pentamers, reduced contacts within the particle, lacks the genome, VP1 and VP2 N-termini, and VP4. Our work provides an understanding of transient SVV structural states and supports the existence of an intermediate SVV A-particle. These findings could help optimize SVV for oncolytic therapy.IMPORTANCESeneca Valley virus (SVV) is a non-enterovirus picornavirus with specific tumor tropism mediated by the receptor Tumor endothelial marker 8, also known as Anthrax toxin receptor 1. Using cryo-electron microscopy, it was possible to identify multiple structural states of SVV. We demonstrate that SVV capsids transition from full particles to altered (A) particles and then to empty-rotated (E^R) particles, with receptor binding and acidic pH driving these conformational changes, respectively. This study also identifies open particles with expelled genomes. Comparisons between A- and E^R-particles reveal that peptide segments of VP1, VP2, and VP4 could potentially play a role in genome delivery. Future work can explore the formation of these structural states <i>in vivo</i>.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0074425"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nsp2 replicase-mediated viral uncoating in porcine alveolar macrophages contributes to the attenuation of PRRSV-2 live attenuated vaccine.","authors":"Yuan-Zhe Bai, Hu Xu, Yong-Gang Liu, Yue Sun, Shi-Jia Xu, Meng-Xin Wang, Qian Wang, Zhi-Jun Tian, Chao-Liang Leng, Gang Wang, Tong-Qing An, Xue-Hui Cai, Hong-Liang Zhang, Yan-Dong Tang","doi":"10.1128/jvi.00636-25","DOIUrl":"10.1128/jvi.00636-25","url":null,"abstract":"<p><p>Type 2 porcine reproductive and respiratory syndrome virus (PRRSV-2) poses a major threat to global swine production. While live attenuated vaccines (LAVs) remain the most effective countermeasure, the molecular mechanisms underlying PRRSV-2 attenuation remain enigmatic. Here, we reveal that PRRSV-2 LAVs exhibit impaired replication in their primary cellular targets-porcine alveolar macrophages (PAMs), with viral uncoating defects being the critical replication barrier. Mechanistically, we identified nonstructural protein 2 (nsp2) as the key viral determinant orchestrating this attenuation phenotype. Strikingly, the substitution of the nsp2 from the vaccine strain into a highly pathogenic PRRSV (HP-PRRSV) significantly attenuated virulence in piglets while maintaining immunogenicity. The chimeric virus elicited robust protective immunity against HP-PRRSV challenge. Our findings elucidated that nsp2-mediated viral uncoating contributes to PRRSV-2 LAV attenuation and established a proof-of-concept strategy for rational PRRSV-2 vaccine design.IMPORTANCELive attenuated vaccines (LAVs) are predominantly used for the management of PRRSV infection; however, limited knowledge exists regarding the mechanisms underlying PRRSV attenuation. Enhancing our understanding of the mechanism by which viruses are attenuated would accelerate the development of optimal live attenuated vaccines against PRRSV. In the present study, we discovered that commercial PRRSV LAVs failed to uncoat inside porcine alveolar macrophages, thereby identifying a novel mechanism by which these LAVs achieve attenuation. Notably, we identified nsp2, a virion protein, as a key factor contributing to the attenuation of PRRSV. Furthermore, we demonstrated that the substitution of the nsp2-coding region with its counterpart derived from a commercial LAV enabled the rapid attenuation of highly virulent strains while providing effective protection against subsequent challenges. Our findings elucidated the feasibility of converting virulent PRRSV into an attenuated vaccine candidate in a timely manner.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0063625"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased infectivity of human cytomegalovirus strain TB40/E conferred by variants of the envelope glycoprotein UL128 and the regulatory protein IE2.","authors":"Xuan Zhou, Linjiang Yang, Giorgia Cimato, Giada Frascaroli, Ana Águeda-Pinto, Laura Hertel, Wolfram Brune","doi":"10.1128/jvi.00642-25","DOIUrl":"10.1128/jvi.00642-25","url":null,"abstract":"<p><p>Human cytomegalovirus (HCMV) infects various cell types in its human host, and this broad tropism plays a vital role in viral transmission, dissemination, and pathogenesis. HCMV strains differ in their ability to infect and replicate in different cell types, but the genetic determinants of cell tropism have only begun to be understood. A widely used HCMV strain, TB40/E, contains a mixture of genetically distinct virus variants. Only a few passages in ARPE-19 epithelial cells resulted in the selective enrichment of a substrain, termed TB40/EE, which infected epithelial cells more efficiently than the parental TB40/E and induced the formation of large multinucleated syncytia. Herein, we used sequence comparison and genetic engineering of a TB40/E-derived bacterial artificial chromosome clone, TB40-BAC4, to demonstrate that the high infectivity of TB40/EE and its ability to induce syncytia in epithelial cells depend on two single-nucleotide variants (SNVs) affecting the envelope glycoprotein UL128 and the major viral transactivator protein, IE2. While the intronic SNV in UL128 increased splicing of the <i>UL128</i> transcript, it surprisingly decreased viral infectivity and replication in epithelial cells. The additional introduction of the IE2 SNV reversed this phenotype, increasing infectivity and syncytium formation. This SNV resulted in a D390H substitution and increased the levels of several early and late viral transcripts, suggesting that it altered the ability of IE2 to activate viral genes. The same two SNVs increased the ability to infect THP-1-derived macrophages and JEG-3 trophoblast cells. These results demonstrate that HCMV cell tropism depends on both envelope glycoproteins and regulatory proteins.IMPORTANCEDifferent genetic versions of human cytomegalovirus (HCMV) affect its ability to infect various human cell types. Here, we focused on a commonly used strain, TB40/E, which contains a mix of virus variants. After growing it in epithelial cells, a specific variant called TB40/EE became dominant. This variant infected epithelial cells more effectively and caused the formation of large, fused cells (syncytia). In this study, we discovered that two small genetic changes were responsible for this behavior. One change affected a protein on the viral envelope (UL128) by altering how its RNA was processed. Surprisingly, this change reduced the virus's ability to spread, but a second change in a regulatory protein (IE2) reversed that effect. Together, these changes enhanced the virus's ability to infect not only epithelial cells but also macrophages and placental cells. This study highlights how small genetic tweaks can influence how HCMV targets different types of human cells.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0064225"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DDX54 drives ALKBH5-mediated demethylation of selected transcripts to suppress interferon antiviral response.","authors":"Hao-Yu Sun, Xiu-Ying Gong, Zi-Ling Qu, Li-Li An, Wen-Hao Guo, Hong-Yu Luan, Meng-Yao Wu, Ji-Cheng Yu, Cheng Dan, Yi-Bing Zhang","doi":"10.1128/jvi.00507-25","DOIUrl":"10.1128/jvi.00507-25","url":null,"abstract":"<p><p>DEAD-box (DDX) proteins are currently reported to shape host innate immunity by regulation of N⁶-methyladenosine (m⁶A) modification of transcripts for host factors involved in antiviral signaling. However, which DDX proteins are involved in antiviral response remains incompletely understood. Here, we identified DDX54 as an inhibitor of type I interferon antiviral response by facilitating m⁶A demethylation of selected transcripts. In the presence of VSV infection, DDX54 overexpression downregulated the interferon response and consequently promoted VSV replication, while DDX54 depletion yielded the opposite effects. Knockout of ALKBH5 revealed that DDX54 downregulated the interferon antiviral response through ALKBH5. VSV infection enabled DDX54 relocation from the nucleolus to the nucleoplasm, where DDX54 and ALKBH5 independently bound to the selected m⁶A-modified transcripts forming m⁶A RNA/protein complexes. Although the total enzymatic activity of cellular ALKBH5 was severely impaired in response to VSV infection, DDX54 interaction with ALKBH5 on the selected transcripts promoted the enzymatic activity of ALKBH5, which, in turn, demethylated these selected transcripts, including <i>mavs</i> mRNA. Consequently, these selected transcripts were largely retained in the nucleus to limit their translation in the cytoplasm, thereby impairing the interferon antiviral response. ATPase activity was essential for DDX54 to bind the selected transcripts and also to promote ALKBH5 demethylase activity. In the absence of VSV infection, DDX54 failed to recognize cellular m⁶A-modified RNAs and barely promoted the enzymatic activity of ALKBH5. Altogether, we conclude that VSV infection activates a DDX54/m⁶A/ALKBH5 axis to fine tune cellular interferon antiviral response by regulating m⁶A modification of the selected transcripts.IMPORTANCEThe m⁶A methylation modification on cellular mRNAs affects many cellular processes, including the innate antiviral response. In this study, we reported that VSV infection facilitated RNA helicase DDX54 to relocate from the nucleolus to the nucleoplasm, where DDX54, together with the m⁶A eraser ALKBH5, bound to a common subset of m⁶A-modified transcripts for host factors involved in antiviral signaling. Such binding promoted the enzymatic activity of ALKBH5 to demethylate the m⁶A modification on these transcripts, therefore limiting their protein translation and consequently impairing interferon antiviral response. Our results reveal an inhibitory function of DDX54 on host innate antiviral response.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0050725"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-assembled cyanidin-3-O-glucoside nanoparticles alleviate inflammation and ferroptosis induced by PRRSV infection.","authors":"Xiaohan Chen, Yipeng Pang, Fructueux Modeste Amona, Zilu Liu, Fang Wang, Yuan Liang, Jiachen Yang, Wanhan Zhang, Xingtang Fang, Xi Chen","doi":"10.1128/jvi.00954-25","DOIUrl":"10.1128/jvi.00954-25","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious pathogen that causes substantial economic losses in the global swine industry, primarily by impairing reproductive performance and respiratory health. However, current therapeutic approaches remain limited in effectively controlling PRRSV infection. Here, we present self-assembled cyanidin-3-O-glucoside (C3G)-based nanoparticles (C3G-Cs-SeNPs) as a promising antiviral agent against PRRSV infection. These nanoparticles demonstrated excellent stability and biocompatibility, with minimal cytotoxicity in Marc-145 cells. C3G-Cs-SeNPs significantly reduced ROS levels in PRRSV-infected cells, enhancing the antioxidant capacity and mitigating oxidative stress. In addition, they effectively inhibited key stages of the PRRSV lifecycle, including viral internalization and replication, leading to a marked decrease in viral proliferation. Moreover, C3G-Cs-SeNPs alleviated ferroptosis by restoring redox homeostasis through enhanced antioxidant enzyme activity. Mechanistically, these nanoparticles potentially activate the SIRT1/Nrf2/HO-1 signaling pathway, which plays a critical role in regulating inflammation and ferroptosis in PRRSV-infected cells. These findings suggest that C3G-Cs-SeNPs could serve as a novel therapeutic approach to modulate inflammation, ferroptosis, and viral replication in respiratory viral infections. Our study highlights the therapeutic potential of C3G-Cs-SeNPs in combating PRRSV infection, with important implications for viral infection management and respiratory disease treatment.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) remains a major challenge in the swine industry, causing significant economic losses due to its high mutation rate and ability to evade host immunity. Current antiviral treatments and vaccines offer limited efficacy, necessitating the development of novel therapeutic strategies. This study introduces self-assembled cyanidin-3-O-glucoside-based chitosan-selenium nanoparticles (C3G-Cs-SeNPs) as a promising antiviral agent. These nanoparticles effectively inhibit PRRSV replication, reduce oxidative stress, and alleviate inflammation and ferroptosis by activating the SIRT1/Nrf2/HO-1 signaling pathway. By mitigating virus-induced cellular damage, C3G-Cs-SeNPs offer a potential therapeutic approach for PRRSV and other respiratory viral infections. This study highlights the role of ferroptosis in PRRSV pathogenesis and presents an innovative nanotechnology-based solution to combat viral infections, contributing to the development of more effective antiviral strategies.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0095425"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and rescue of porcine bastroviruses associated with polioencephalomyelitis in domestic pigs.","authors":"Nicole Wildi, Stefano Bagatella, Xuanxuan Zhang, Mark C Hawes, Kara L D Dawson, Honglei Chen, Som Walker, Gemma Harvey, Brenda van der Heide, David T Williams, Andrew Hemphill, Corinne Gurtner, Jianning Wang, Torsten Seuberlich","doi":"10.1128/jvi.01130-25","DOIUrl":"10.1128/jvi.01130-25","url":null,"abstract":"<p><p>Bastroviruses (BastV) are non-enveloped single-stranded positive-sense RNA viruses that have been discovered recently in feces samples of different animals and humans. The non-structural proteins of these viruses show similarities to those of hepevirids (<i>Hepeviridae</i>), and the structural proteins exhibit similarities to those of astrovirids (<i>Astroviridae</i>). BastVs have been found in fecal samples of mammals, amphibians, and invertebrates, but the association of infection and clinical disease manifestations has not been established. Here, we report the identification of porcine bastroviruses (PoBastV) in central nervous system (CNS) tissue samples of domestic pigs that presented fatal neurological disease in two unrelated disease outbreak scenarios in Australia and Switzerland. Viral metatranscriptomics of formalin-fixed paraffin-embedded (FFPE) CNS tissues identified genomic sequences of two genetically closely related PoBastV strains (PoBastV AUS/2015 and CHE/2022). Genomic RNA of both strains was readily detected by <i>in situ</i> RNA hybridization in neurons and glial cells of CNS tissues presenting histopathological lesions, thus supporting a plausible causal relationship between neurotropism and disease. We generated a molecular cDNA clone of PoBastV CHE/2022 and rescued infectious virus by reverse genetics in swine kidney cells (SK6) and further virus passage in intestinal porcine enterocytes (IPEC-J2). We used transmission electron microscopy to demonstrate PoBastV CHE/2022 virions in infected IPEC-J2 cells. These findings pave the way toward PoBastV as one of the etiologies of neurological disease outbreaks. Additionally, they allow studies further elucidating the molecular biology and pathogenesis of emerging BastV infections.IMPORTANCEBastroviruses (BastV) have been discovered recently in feces samples of different animals and humans. To date, BastV infections have not been associated with clinical diseases. Here, we report the identification of porcine BastV (PoBastV) in central nervous system tissue samples of domestic pigs that presented fatal neurological disease in two unrelated disease outbreak scenarios in Australia and Switzerland. This finding supports the hypothesis that PoBastV infections may cause clinical disease. We further rescued infectious PoBastV <i>in vitro</i> using the genome sequence data of one neuroinvasive PoBastV strain. With these tools, we can now start deciphering the molecular biology of BastV replication and the interaction of the virus with the host, which will lay the ground for future prophylactic and therapeutic strategies.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0113025"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of the pre-membrane and envelope proteins on structure, pathogenicity, and tropism of tick-borne encephalitis virus.","authors":"Ebba Rosendal, Kyrylo Bisikalo, Stefanie M A Willekens, Marie Lindgren, Jiří Holoubek, Pavel Svoboda, Amanda Lappalainen, Ebba Könighofer, Ekaterina Mirgorodskaya, Rickard Nordén, Federico Morini, William Rosenbaum, Daniel Růžek, Ulf Ahlgren, Maria Anastasina, Andres Merits, Sarah J Butcher, Emma Nilsson, Anna K Överby","doi":"10.1128/jvi.00870-25","DOIUrl":"10.1128/jvi.00870-25","url":null,"abstract":"<p><p>Tick-borne encephalitis virus (TBEV) is a neurotropic flavivirus that causes thousands of human infections annually. Viral tropism in the brain is determined by the presence of necessary receptors, entry factors, and the ability of the virus to overcome host defenses. The viral structural proteins, pre-membrane (prM), and envelope (E) play an important role in receptor binding, membrane fusion, particle maturation, and antibody neutralization. To understand how these proteins influence virus distribution and tropism in the brain, we generated a chimeric virus harboring the prM and ectodomain of E from TBEV in the background of the low-pathogenic Langat virus (LGTV). We solved the atomic structures of both the chimeric virus and LGTV to compare them to the known TBEV structure. We show that this chimeric virus remains low-pathogenic, while being structurally and antigenically similar to TBEV. Using 3D optical whole brain imaging combined with immunohistochemistry, we found that both LGTV and the chimeric virus primarily infect the cerebral cortex, with no significant differences in their localization or tropism. In contrast, TBEV shows high infection of the cerebellum and a strong preference toward Purkinje cells, indicating that factors other than the prM and E proteins are important for determining TBEV tropism in the brain. Together, this provides new insights into the roles of the structural and non-structural proteins of tick-borne flaviviruses.</p><p><strong>Importance: </strong>Although an effective vaccine exists, there is no treatment for those infected by the tick-borne encephalitis virus (TBEV). This study aimed to better understand how the virus's surface proteins influence viral tropism and pathogenicity. We created a chimeric virus with prM and E proteins of TBEV in the genetic background of the low-pathogenic Langat virus (LGTV). The chimeric virus remained low pathogenic, similar to LGTV. Both viruses infected similar brain regions, while TBEV showed a strong preference for the cerebellum and Purkinje cells. This means that other parts of the virus, such as non-structural proteins or NCR, likely decide how the virus behaves in the brain. This study also presents the first cryogenic electron microscopy structure of LGTV, the first whole-brain imaging of TBEV infection in mouse brain, and a new model system to study surface proteins in tick-borne flaviviruses-laying groundwork for future studies on viral tropism, antibody cross-reactivity, and virus-receptor interaction.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0087025"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}