Virologica Sinica最新文献

{"title":"The expression of CD39 on NK cells relates to poor HIV-1 suppression in treatment-naïve HIV-1-infected individuals: Association with elevated IL-10 secretion and TIGIT co-expression","authors":"Xin Zhang ,&nbsp;Qianqian Xu ,&nbsp;Junyan Jin ,&nbsp;Hongxia Yan ,&nbsp;Xiaofan Lu ,&nbsp;Zhen Li ,&nbsp;Zhiying Liu ,&nbsp;Rui Wang ,&nbsp;Lin Yuan ,&nbsp;Zhenglai Ma ,&nbsp;Tong Zhang ,&nbsp;Hao Wu ,&nbsp;Bin Su","doi":"10.1016/j.virs.2026.03.006","DOIUrl":"10.1016/j.virs.2026.03.006","url":null,"abstract":"<div><div>CD39 exerts an inhibitory effect on tumour progression by impairing the cytotoxic capacity of natural killer (NK) cells against cancer cells. However, the impact of CD39 expression on the non-cytolytic functions of NK cells in treatment-naïve human immunodeficiency virus type 1 (HIV-1)-infected individuals remains poorly understood. In this study, thirty-four individuals with acute HIV-1 infection (AHI), thirty-eight with chronic HIV-1 infection (CHI), and twenty-four HIV-1-negative healthy controls (HC) were enrolled to explore the role of CD39 expression on NK cells in HIV-1 suppression at different infection stages. Flow cytometry was employed to analyze the immune phenotype and functional characteristics of NK cells. We found that CD39 expression on NK cells was significantly upregulated following HIV-1 infection, and its positive rate was positively associated with HIV-1 viral load in both AHI and CHI individuals. Compared with CD39⁻ NK cells, CD39⁺ NK cells exhibited reduced activation; in AHI individuals, the activation level of CD39⁺ NK cells was positively associated with HIV-1 viral load but inversely correlated with CD4⁺ T-cell counts. In CHI individuals, the interleukin-10 (IL-10)-producing capacity of total NK cells, CD39⁺ NK cells, and CD39⁻ NK cells was enhanced and positively correlated with HIV-1 viral load. Additionally, across the AHI and CHI groups, the overall IL-10-secreting ability of NK cells was positively correlated with the frequency of CD39⁺ NK cells. In both AHI and CHI individuals, CD39⁺ NK cells showed lower T-cell immunoglobulin and ITIM domain (TIGIT) expression than CD39⁻ NK cells, while the CD39⁺TIGIT⁺ NK cell subset displayed significantly stronger IL-10-secreting capacity. POM-1, an inhibitor of CD39 ectonucleotidase activity, could enhance IL-10 secretion by NK cells in both HIV-1-infected individuals and the majority of healthy controls, but attenuate interferon-γ (IFN-γ) secretion by NK cells in HIV-1-infected individuals. In contrast, the CD39-blocking antibody A1 reduced IFN-γ secretion without affecting IL-10 secretion by NK cells in both HIV-1-infected individuals and healthy controls. Our findings reveal a novel CD39⁺ NK cell-associated mechanism that contributes to ineffective HIV-1 control, and suggest that CD39, alone or combined with TIGIT, may serve as a promising target to restore antiviral NK cell function in treatment-naïve individuals living with HIV-1.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 293-302"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494458","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 ,&nbsp;Junnan Lu ,&nbsp;Zirong Han ,&nbsp;Zhishan Fan ,&nbsp;Xinru Hu ,&nbsp;Lichuang Jiao ,&nbsp;Lisha Deng ,&nbsp;Wenming Liu ,&nbsp;Junqi Liu ,&nbsp;Weiqi Pan ,&nbsp;Ling Chen ,&nbsp;Liqiang Feng ,&nbsp;Caijun Sun","doi":"10.1016/j.virs.2026.04.004","DOIUrl":"10.1016/j.virs.2026.04.004","url":null,"abstract":"<div><div>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 (<em>G</em>) gene deleted (rVSVΔG) and another with the <em>L</em> 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.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 423-438"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","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":"Emergence of a novel H4N6 avian influenza virus with mammalian adaptation isolated from migratory birds in Zhejiang Province, China, 2024","authors":"Yongchun Yang ,&nbsp;Han Liu ,&nbsp;Yaling Li ,&nbsp;Lin Liu ,&nbsp;Tiantian Chen ,&nbsp;Jiahao Zhang","doi":"10.1016/j.virs.2026.03.005","DOIUrl":"10.1016/j.virs.2026.03.005","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 466-469"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463919","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 of a novel HIV-1 circulating recombinant form (CRF161_0107) from CRF01_AE-C5 lineage among men who have sex with men in southwestern China","authors":"Min Chen ,&nbsp;Huichao Chen ,&nbsp;Yanling Ma ,&nbsp;Manhong Jia ,&nbsp;Wenfei Ding","doi":"10.1016/j.virs.2026.03.008","DOIUrl":"10.1016/j.virs.2026.03.008","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 470-473"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499852","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 ,&nbsp;Yingyi Chen ,&nbsp;Shanyao Du ,&nbsp;Xiumei Huang ,&nbsp;Yuhuan Shao ,&nbsp;Jiangwu Huang ,&nbsp;Ming Liao ,&nbsp;Manman Dai","doi":"10.1016/j.virs.2026.04.008","DOIUrl":"10.1016/j.virs.2026.04.008","url":null,"abstract":"<div><div>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 <em>in vitro</em>. 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 <em>in ovo</em> (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 <em>IFN-α</em>, <em>IFN-β</em>, <em>IFN-γ</em>, <em>IL-2</em>, <em>IL-5</em>, <em>IL-6</em>, <em>IL-10</em>, and <em>IL-13</em>. Furthermore, ELISPOT assays confirmed enhanced <em>IFN-γ</em> 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 <em>in ovo</em> strategy provides a viable hatchery intervention, the subcutaneous route exhibits the superior immune activation and protection compared with conventional InV alone.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 455-465"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","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":"ZNF219 inhibits porcine epidemic diarrhea virus by degrading viral S2 protein","authors":"Wenli Zhao ,&nbsp;Ning Kong ,&nbsp;Daoliang Lan ,&nbsp;Yu Zhang ,&nbsp;Hailong Liu ,&nbsp;Chunyun Liu ,&nbsp;Wenzhen Qin ,&nbsp;Xinyu Yang ,&nbsp;Tian Liu ,&nbsp;Wu Tong ,&nbsp;Hai Yu ,&nbsp;Hao Zheng ,&nbsp;Guangzhi Tong ,&nbsp;Shengsong Xie ,&nbsp;Guangxu Xing ,&nbsp;Tongling Shan","doi":"10.1016/j.virs.2026.03.007","DOIUrl":"10.1016/j.virs.2026.03.007","url":null,"abstract":"<div><div>Since its discovery, porcine epidemic diarrhea virus (PEDV) has significantly affected the agricultural economy worldwide. The available commercialized coronavirus vaccines cannot adequately control emerging strains. Therefore, investigating the correlation between viruses and antiviral host factors is necessary. In this study, we showed that zinc finger protein 219 (ZNF219) was upregulated by viral nonstructural protein 12 (nsp12) upon PEDV challenge. Moreover, ZNF219 inhibited the replication of PEDV through selective autophagic degradation of the PEDV S2 protein. ZNF219 recruited TRAF6, the ubiquitin E3 ligase, to ubiquitinate the PEDV S2 protein. After recognition, the ubiquitinated PEDV S2 protein was delivered to autolysosomes via the cargo receptor p62 for degradation by autophagy, thus inhibiting the proliferation of PEDV. To summarize, after sensing PEDV infection by recognizing the viral nsp12 protein, host cells upregulated the intracellular expression of ZNF219, which degraded the viral S2 protein by activating autophagy, thus suppressing viral replication. Our study revealed a novel antiviral mechanism involving ZNF219 and provided a novel target for preventing and treating PEDV.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 303-313"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499847","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 ,&nbsp;Qian-tong Jin ,&nbsp;Xiao-min Zhang ,&nbsp;Xiao-chen Bo ,&nbsp;Zi-lin Ren ,&nbsp;Yi-gang Tong ,&nbsp;Ming Ni","doi":"10.1016/j.virs.2026.03.015","DOIUrl":"10.1016/j.virs.2026.03.015","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 382-391"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","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":"Cepharanthine hydrochloride alleviates herpesvirus encephalitis by inhibiting Nrf2 degradation","authors":"Qiongzhen Zeng ,&nbsp;Weixiangmin Zou ,&nbsp;Jiaqi Wu ,&nbsp;Menghe Li ,&nbsp;Zexu Wang ,&nbsp;Caiwenjie La ,&nbsp;Cuifang Ye ,&nbsp;Zhe Ren ,&nbsp;Yifei Wang ,&nbsp;Kai Zheng","doi":"10.1016/j.virs.2026.03.016","DOIUrl":"10.1016/j.virs.2026.03.016","url":null,"abstract":"<div><div>Herpes simplex virus type 1 (HSV-1) infection can induce herpes simplex encephalitis (HSE), a life-threatening neurological disorder characterized by active viral replication within the central nervous system accompanied by excessive neuroinflammatory responses. Cepharanthine hydrochloride (CH) is a natural bisbenzylisoquinoline alkaloid with diverse pharmacological activities. CH was evaluated for its antiviral and anti-inflammatory activities against HSV-1 infection. In microglia, CH markedly inhibited viral replication and suppressed STING-NF-κB signaling, thereby reducing HSV-1-associated neuroinflammation. During HSV-1 infection, CH binds to Nrf2, disrupting Keap1-Nrf2 interaction and subsequent ubiquitination. This hindered Nrf2 degradation and attenuated STING activation. In an HSE mouse model, CH significantly reduced viral loads in brain tissue, improved survival rates, prevented weight loss, and alleviated neurological symptoms. Furthermore, CH promoted the accumulation of Nrf2 and inhibited the STING-NF-κB signaling pathway <em>in vivo</em>. Collectively, these results indicate that CH represents a potential antiviral strategy for HSE.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 392-403"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616882","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":"Corrigendum to “African swine fever virus MGF360-9L degrades DDX20 through the Rab1A-dependent autophagy pathway to antagonize its antiviral effect” [Virol. Sin. 40 (2025) 822–834]","authors":"Lu He ,&nbsp;Xuxu Fan ,&nbsp;Zhaoyu Zhu ,&nbsp;Danshi Pei ,&nbsp;Yizhuo Wang ,&nbsp;Xizhong Li ,&nbsp;Qingfeng Ren ,&nbsp;Haixue Zheng ,&nbsp;Weiwei Li ,&nbsp;Zixiang Zhu","doi":"10.1016/j.virs.2026.03.004","DOIUrl":"10.1016/j.virs.2026.03.004","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 490-491"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515064","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 ,&nbsp;Ran Tao ,&nbsp;Xi Cheng ,&nbsp;Hui Deng ,&nbsp;Jianxin Wang ,&nbsp;Xianyu Bian ,&nbsp;Jinzhu Zhou ,&nbsp;Xuejiao Zhu ,&nbsp;Min Sun ,&nbsp;Xuehan Zhang ,&nbsp;Mi Hu ,&nbsp;Rongli Guo ,&nbsp;Wei Wang ,&nbsp;Siyuan Ding ,&nbsp;Bin Li","doi":"10.1016/j.virs.2026.04.005","DOIUrl":"10.1016/j.virs.2026.04.005","url":null,"abstract":"<div><div>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 <em>in vivo</em>, 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.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 439-454"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","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}