Virologica Sinica最新文献

{"title":"Two orthobunyaviruses: OYAV and EBIV co-opt the AhR-CYP1A1 axis to suppress type I interferon responses.","authors":"Qianyun Hu, Fei Wang, Xiaoyu Wang, Xiaokui Li, Zhiming Yuan, Maohua Zhong, Han Xia","doi":"10.1016/j.virs.2026.04.001","DOIUrl":"10.1016/j.virs.2026.04.001","url":null,"abstract":"<p><p>The type I interferon (IFN-I) system serves as a frontline defense against viral infection, yet how orthobunyaviruses counteract this pathway remains poorly defined. Here, we identify cytochrome P450 1A1 (CYP1A1) as a crucial host factor promoting infection by two emerging orthobunyaviruses-Oya virus (OYAV) and Ebinur Lake virus (EBIV). Transcriptomic and functional analyses demonstrate that CYP1A1 overexpression enhances viral RNA synthesis, whereas its CRISPR-Cas9-mediated knockout attenuates infection. Mechanistically, OYAV and EBIV activate the aryl hydrocarbon receptor (AhR), driving its nuclear translocation and subsequent upregulation of CYP1A1. Deficiency of CYP1A1 potentiates IFN-β production and interferon-stimulated gene (ISG) expression, while its overexpression suppressed antiviral signaling, revealing an immunomodulatory role that is distinct from its canonical metabolic function. Collectively, this work defines the AhR-CYP1A1 axis as a conserved immune-evasion module exploited by emerging orthobunyaviruses and highlights the innate immune pathway as a potential therapeutic target against these emerging threats.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HVT-based multiepitope vaccine administered subcutaneously or in ovo boosts protection of inactivated H9N2 vaccine against heterologous virus.","authors":"Zimin Xie, Yingyi Chen, Shanyao Du, Xiumei Huang, Yuhuan Shao, Jiangwu Huang, Ming Liao, Manman Dai","doi":"10.1016/j.virs.2026.04.008","DOIUrl":"10.1016/j.virs.2026.04.008","url":null,"abstract":"<p><p>H9N2 avian influenza virus (AIV) poses a persistent threat as inactivated vaccines (InV) often fail to prevent viral shedding. To address this, we developed a recombinant turkey herpesvirus (HVT-BNT) expressing conserved B and T cell epitopes from H9N2 AIV to enhance both humoral and cellular immunity. HVT-BNT exhibited genetic stability over 15 serial passages and growth kinetics comparable to the parental strain in vitro. We evaluated immunization strategies of HVT-BNT combined with InV in 1-day-old chicks and 18-day-old embryos via subcutaneous (HVT-BNT + InV) or in ovo (HVT-BNT-ovo + InV) routes, respectively. Compared to InV alone, HVT-BNT + InV elicited significantly higher HI and neutralizing antibody titers, elevated IgG and IgM levels, and increased proportions of CD8⁺ T cells. Similarly, the HVT-BNT-ovo + InV group exhibited a trend of higher values in these indicators. Notably, while the InV group displayed no significant differences in key immune cytokines compared to the control group, the combined immunization groups exhibited significant upregulation of IFN-α, IFN-β, IFN-γ, IL-2, IL-5, IL-6, IL-10, and IL-13. Furthermore, ELISPOT assays confirmed enhanced IFN-γ secretion in response to conserved AIV peptides (NP_380-393, NP_455-463, and NS1_98-106) in the combined immunization groups. Following heterologous H9N2 AIV challenge, oropharyngeal positivity rates in the combined immunization groups were lower than those in the InV group at 5 DPI. Similarly, cloacal positivity rates were more reduced in the combined groups compared to the InV group at 3 and 5 DPI. By 7 DPI, viral shedding was completely cleared in both combined immunization groups, whereas the InV group continued to shed virus via the oropharyngeal route. These findings demonstrate that the HVT-BNT-based vaccination strategy effectively enhances both humoral and cellular immune responses, providing superior early protection. While the in ovo strategy provides a viable hatchery intervention, the subcutaneous route exhibits the superior immune activation and protection compared with conventional InV alone.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STING1 negatively regulates translation and replication of foot-and-mouth disease virus independently of interferon and is antagonized by the viral proteins 3C and 2B.","authors":"Wenhua Shao, Wei Zhang, Zhitong Chen, Tingting Zhou, Xiaoyi Zhao, Hongyi Liu, Chuangwei Chen, Xingyan Dong, Weijun Cao, Zongsheng Zhao, Fan Yang, Zixiang Zhu, Haixue Zheng","doi":"10.1016/j.virs.2026.04.007","DOIUrl":"10.1016/j.virs.2026.04.007","url":null,"abstract":"<p><p>Foot-and-mouth disease virus (FMDV), a highly contagious picornavirus, employs multifaceted strategies to evade host innate immunity, with viral proteins 3C protease (3C^pro) and 2 B serving as key immune antagonists. The stimulator of interferon genes 1 (STING1) is a critical innate immune adaptor; however, its role and regulatory mechanisms during FMDV infection remain incompletely understood. Here, we report that STING1 inhibits FMDV replication through an interferon (IFN)-independent mechanism, while FMDV counteracts this antiviral effect by degrading STING1 via 3C^pro and 2B. Mechanistically, FMDV 3C^pro mediates STING1 degradation in a protease activity-dependent manner; this STING1-degrading activity is conserved among 3C^pro proteins of poliovirus, enterovirus 71, and coxsackievirus, but not senecavirus A. In contrast, FMDV 2B suppresses STING1 expression at the mRNA level, and neither proteasomal, lysosomal, nor caspase pathways are involved in 3C^pro/2B-mediated STING1 downregulation. Furthermore, the STING1 stabilizer SB24011 enhances endogenous STING1 expression, dose-dependently inhibits FMDV replication by targeting viral internal ribosome entry site (IRES)-mediated translation, and exhibits broad-spectrum antiviral activity against multiple picornaviruses. In vivo, SB24011 treatment alleviates virus-induced histopathological lesions. Collectively, our findings reveal a novel IFN-independent antiviral role of STING1 against FMDV, identify 3C^pro and 2B as FMDV-encoded STING1 antagonists, and highlight the potential of SB24011 as a broad-spectrum anti-picornavirus therapeutic agent.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A natural five-amino-acid insert at the S2' cleavage site of MERS-CoV spike enhances viral membrane fusion.","authors":"Guimin Dai, Wenjie Chen, Wenying Cao, Guigen Zhang","doi":"10.1016/j.virs.2026.04.006","DOIUrl":"10.1016/j.virs.2026.04.006","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of G9 genotype porcine rotavirus using reverse genetics system and its application for antiviral screen and vaccine development.","authors":"Nan Han, Ran Tao, Xi Cheng, Hui Deng, Jianxin Wang, Xianyu Bian, Jinzhu Zhou, Xuejiao Zhu, Min Sun, Xuehan Zhang, Mi Hu, Rongli Guo, Wei Wang, Siyuan Ding, Bin Li","doi":"10.1016/j.virs.2026.04.005","DOIUrl":"10.1016/j.virs.2026.04.005","url":null,"abstract":"<p><p>Group A rotaviruses (RVs) continue to be one of the most important pathogens causing severe acute gastroenteritis in infants and young animals worldwide. Recently, the prevalence of porcine RV (PoRV) from pig farms has strikingly increased, adversely affecting the swine industry, particularly with the G9 genotype of PoRV VP7 emerging as the predominant genotype spreading in China. Current vaccines against PoRV fail to provide sufficient protective immunity, necessitating urgent development of effective vaccines and antiviral drugs against PoRV. Here, we successfully established and improved the entirely plasmid-based reverse genetics (RG) system to rescue a G9 genotype of recombinant PoRV AHFY2022 strain (G9P[23]). Using the improved RG system, we rescued recombinant AHFY2022 harboring the fluorescent UnaG protein or nano-luciferase (NLuc) reporter within gene segment 7 that encodes non-structural protein 3 (NSP3). Furthermore, we adopted the UnaG reporter virus to screen anti-PoRV drugs and identified two promising antiviral drugs, C8 and C9. Moreover, we generated the recombinant PoRV (rAHFY2022-G5-VP7) containing G5 genotype of VP7 from PoRV-positive samples in the backbone of AHFY2022 strain. The reassortant strain exhibited efficient replication and genetic stability. Mouse models were utilized to evaluate the immune responses elicited by rAHFY2022-G5-VP7 strain in vivo, revealing similar neutralizing antibodies and cellular immune response compared to the parental AHFY2022 strain in mice. Together, this study provides an important tool for screening potential anti-PoRV drugs and developing novel vaccines against prevalent PoRV strains.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A semi-replicating VSV (srVSV)-based platform for developing broad-spectrum mucosal vaccines against influenza A viruses.","authors":"Xianmiao Ye, Junnan Lu, Zirong Han, Zhishan Fan, Xinru Hu, Lichuang Jiao, Lisha Deng, Wenming Liu, Junqi Liu, Weiqi Pan, Ling Chen, Liqiang Feng, Caijun Sun","doi":"10.1016/j.virs.2026.04.004","DOIUrl":"10.1016/j.virs.2026.04.004","url":null,"abstract":"<p><p>Influenza A viruses (IAVs) are significant respiratory pathogens characterized by high mutation rates and frequent genetic reassortments, underscoring the need for vaccines that can induce robust and broadly protective mucosal immunity. While replication-competent vesicular stomatitis virus (VSV) vectors have the potential to elicit mucosal immunity, their neurovirulence raises significant safety concerns. Herein, we report that a semi-replicating VSV (srVSV) vector, composed of one VSV with the glycoprotein (G) gene deleted (rVSVΔG) and another with the L gene deleted (rVSVΔL), has improved safety. Using srVSV, we constructed a monovalent vaccine (srVSV-N1), expressing the neuraminidase 1 (N1) of IAV. A single intranasal dose of srVSV-N1 elicited both systemic and mucosal immune responses against N1, and provided sterilizing immunity against homologous influenza virus. We further generated a bivalent IAV vaccine (srVSV-N1/N2), co-expressing N1 and N2. A single intranasal dose of srVSV-N1/N2 conferred 80% protection against heterologous IAVs (H1N1 and H3N2). Notably, low-dose priming immunization followed by a high-dose boost with srVSV-N1/N2 fully protected mice against lethal heterologous IAV challenges. These findings demonstrate the potential of the srVSV platform for developing mucosal vaccines against IAVs and other respiratory viruses.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of a novel ulcerative enteritis-associated adenovirus of quail causing cross-species infection in chickens.","authors":"Hui Tang, Yin Shi, Qing Zhang, Fei Zhu, Jia-Yao Hou, Jing-Ying Liao, Yi-Shuai Zhang, Chang-Xin Jing, Xin-Qi Liu, Chao-Ting Xiao","doi":"10.1016/j.virs.2026.04.002","DOIUrl":"10.1016/j.virs.2026.04.002","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanobody targeting glycan cap confers broad orthoebolavirus neutralization.","authors":"Xinhui Zhang, Yi Liao, Xiuying Liu, Jingya Zhou, Peixiang Gao, Xuemeng Dong, Shengnan Pan, Huarui Duan, Junyu Liu, Xiaojing Chi, Wei Yang","doi":"10.1016/j.virs.2026.03.018","DOIUrl":"10.1016/j.virs.2026.03.018","url":null,"abstract":"<p><p>The Zaire Ebola virus (EBOV) and Bundibugyo virus (BDBV) cause severe hemorrhagic fever with high mortality, highlighting the urgent need for broad-spectrum antiviral therapies. Neutralizing nanobodies, with their small size, structural stability, and ability to access sterically restricted epitopes, represent a promising antiviral modality. Here, we identified a high-affinity nanobody, BDBV-Nb02, from a fully synthetic phage display library targeting the glycan cap of BDBV glycoprotein (GP1). BDBV-Nb02 demonstrated strong binding kinetics (KD ≈ 1 nM) and potent neutralizing activity against both BDBV and EBOV pseudoviruses, with half-maximal inhibitory concentration (IC₅₀) values in the nanomolar range. Engineering a bivalent format significantly enhanced neutralization potency, achieving up to a 56-fold reduction in the 90% inhibitory concentration (IC₉₀) compared with the monovalent form. Epitope competition assays and molecular docking revealed that BDBV-Nb02 targets a conserved glycan cleft, with residues F248 and NP278/279 identified as critical neutralization sites. In contrast, Fc-fusion constructs impaired the nanobody's efficacy, highlighting the importance of preserving the structural features that enable access to glycan-shielded epitopes. Our findings demonstrate that BDBV-Nb02 is a promising candidate for broad-spectrum orthoebolavirus therapy and may serve as a valuable component in future antiviral cocktail formulations.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic-epidemiological analysis of 15 million SARS-CoV-2 genomes reveals accelerated fitness gain of JN.1 lineage.","authors":"Zhong-Yi Lei, Qian-Tong Jin, Xiao-Min Zhang, Xiao-Chen Bo, Zi-Lin Ren, Yi-Gang Tong, Ming Ni","doi":"10.1016/j.virs.2026.03.015","DOIUrl":"10.1016/j.virs.2026.03.015","url":null,"abstract":"<p><p>The evolution of SARS-CoV-2 has been driven by successive globally circulating waves, including the Alpha and Delta lineages, early Omicron (BA.1-BA.5), XBB, and the recently dominant JN.1 lineages. Although the marked advantage in fitness of early Omicron over Delta lineages has been recognized, there is a lack of systematic evaluation of SARS-CoV-2 fitness across 2020 to 2025. Here, we analyzed 15.23 million SARS-CoV-2 genomes available through May 2025. The accumulation of mutations in the spike protein of the virus has continued to accelerate over time, whereas the trend slowed in the other viral proteins. Using a Bayesian genomic-epidemiological framework, we estimated that lineage fitness increased approximately linearly from 2021 to 2025. Notably, JN.1 lineages exhibited a significantly higher rate of fitness gain than their predecessor XBB and earlier Omicron lineages. We further analyzed characteristic mutations of JN.1 and found that those in the receptor-binding domain were associated with larger alterations in residue hydropathy, charge, and structural surface exposure relative to other lineages. These findings suggest JN.1 as a distinct evolutionary stage and underscore the importance of sustained genomic surveillance.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of severe in vitro and in vivo infection models for coxsackievirus B4 and their application in identifying viral virulence determinants.","authors":"Haoyi Liu, Xianglin Xuan, Bizhen Tang, Huan Wang, Li Zhang, Shuyan Qiu, Chuncong Mo, Xiao Li, Xingui Tian, Rong Zhou, Qian Liu, Wenkuan Liu","doi":"10.1016/j.virs.2026.04.003","DOIUrl":"10.1016/j.virs.2026.04.003","url":null,"abstract":"<p><p>Coxsackievirus B4 (CVB4) is a highly pathogenic enterovirus associated with severe neurological disease and mortality. To establish research models that recapitulate severe CVB4 infection, two clinical isolates with distinct neurovirulence-the high-virulence strain GZ-HFM01 and low-virulence strain GZ-R6-were used. An in vitro neurocytotoxicity model with human neuroblastoma SH-SY5Y cells showed that GZ-HFM01 produced significantly larger plaques than GZ-R6, reflecting its increased capacity to damage neuronal cells. Concurrently, an optimized in vivo severe infection model was established in 3-day-old ICR mice through intraperitoneal inoculation, which reproduced key clinical features of severe disease. Compared with GZ-R6, GZ-HFM01 infection resulted in significantly reduced survival, progressive neurological impairment, time-dependent viral accumulation in brain tissue, pronounced histopathological injury, and elevated serum pro-inflammatory cytokine levels. To map genomic determinants of neurovirulence, a chimeric virus panel was generated by replacing individual genome segments (5'untranslated region [UTR], P1, P2, P3, or 3'UTR) of GZ-HFM01 with the corresponding regions from GZ-R6. Evaluation with the established models demonstrated that replacement of the P2 region significantly attenuated both the cytopathic effect in SH-SY5Y cells and pathogenicity in 3-day-old ICR mice. Animal studies further indicated that substitution of the 5'UTR or P1 region also reduced virulence-a phenotype absent from the cell-based model-underscoring the multifactorial regulation of CVB4 pathogenesis. In conclusion, this study provides validated in vitro and in vivo models of severe CVB4 infection and identifies key genomic segments that contribute to neurovirulence, offering a foundation for mechanistic research and the development of targeted interventions against severe CVB4-induced disease.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}