Virologica Sinica最新文献

{"title":"Tupaia belangeri better reflects the typical symptoms of Chikungunya virus infection than mice: A comparative study","authors":"Yan Guo,&nbsp;Mengyuan Zheng,&nbsp;Qi Wang,&nbsp;Hui Xiao,&nbsp;Li Liu,&nbsp;Shuwei Dong,&nbsp;Yonghan Luo,&nbsp;Zhouling Pan,&nbsp;Yujie Xiang,&nbsp;Yanxian Jiang,&nbsp;Xiao Chen,&nbsp;Hailin Tang,&nbsp;Yuemei Feng,&nbsp;Yue Feng,&nbsp;Xueshan Xia","doi":"10.1016/j.virs.2026.03.013","DOIUrl":"10.1016/j.virs.2026.03.013","url":null,"abstract":"<div><div>Chikungunya virus (CHIKV) infection in humans is typically characterized by acute febrile illness, rash, and polyarthralgia, and often progresses to chronic arthralgia. However, existing small-animal models fail to capture both the acute and chronic phases of the disease. In this study, we compared Chinese tree shrews (<em>Tupaia belangeri</em>) and C57BL/6 mice in terms of infection dynamics, viral characteristics, histopathological changes, and immune responses. Following dual-site inoculation (subcutaneous injection into the abdomen and footpad), <em>Tupaia belangeri</em> exhibited typical symptoms that more closely resembled those of humans, including pronounced fever, foot swelling, and skin lesions, and were accompanied by higher and more sustained viral loads in blood and multiple tissues. Histopathological examination revealed marked inflammation and tissue damage in muscle and joint tissues, consistent with pathological changes observed in humans. Transcriptomic analysis further demonstrated significant upregulation of multiple key immune-related genes (<em>CXCL10, ISG15, IFIT3, SERPING1, MCEMP1, IFI6</em>), indicating a human-like immune response profile. Collectively, our results show that <em>Tupaia belangeri</em> faithfully mirrors the infection features, viral dynamics, and immune responses of human CHIKV infection, establishing it as a valuable model for dissecting disease mechanisms and testing vaccines or antiviral therapies.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 753-765"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood and gut virome remodeling in gastric cancer: Anellovirus expansion and novel virus discovery","authors":"Yi Zhou,&nbsp;Qing Guo,&nbsp;Xingyue Zhao,&nbsp;Wei Zhang,&nbsp;Han Zhang,&nbsp;Shiyin Huang,&nbsp;Zihan He,&nbsp;Youhua Xie,&nbsp;Wen Zhang,&nbsp;Jinhua Gu,&nbsp;Shaokun Pan,&nbsp;Wang Li","doi":"10.1016/j.virs.2026.08.010","DOIUrl":"10.1016/j.virs.2026.08.010","url":null,"abstract":"<div><div>Gastric cancer (GC) is a prevalent malignancy worldwide, yet effective early diagnostic tools remain lacking, and the role of the virome, a key component of the tumor microenvironment, in GC progression is largely unknown. This study aimed to characterize the virome landscapes in peripheral blood and feces of GC patients versus healthy controls, and to identify viral signatures associated with GC onset and metastasis. We performed viral metagenomic sequencing on pooled libraries from 100 GC patients (45 non-metastatic, 55 metastatic) and 50 healthy controls, followed by taxonomic annotation, diversity assessment, LEfSe differential abundance testing, and co-occurrence network analysis. In blood, the GC virome shifted from a bacteriophage-dominated profile in controls to one overwhelmingly dominated by <em>Anelloviridae</em> (&gt; 80%), with significantly decreased alpha diversity. In contrast, the gut virome of GC patients showed increased alpha diversity and coexistence of diverse bacteriophages. LEfSe identified betatorquevirus in blood as a key discriminatory taxon for GC. Network analysis revealed negative correlations between <em>Anelloviridae</em> and multiple bacteriophage families, suggesting niche competition. We also discovered 67 provisional novel anellovirus species and one novel gemykibivirus in GC patient blood. Collectively, our findings indicate that GC is associated with compartment-specific virome remodeling in blood and gut, and that expansion of blood anelloviruses holds promise as a non-invasive biomarker. This study provides a foundational resource for understanding the virome's role in GC.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 791-805"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Cover","authors":"","doi":"10.1016/S1995-820X(26)00152-5","DOIUrl":"10.1016/S1995-820X(26)00152-5","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Page OFC"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MMF inhibits poxvirus infection by disrupting IMPDH2 interaction with USP5 and inducing its rod-and-ring assemblies","authors":"Qian Sun,&nbsp;Kesen Liu,&nbsp;Wandi Cao,&nbsp;Chengyue Wu,&nbsp;Hanhua Zhang,&nbsp;Xingya Wang,&nbsp;Chen Peng,&nbsp;Jie Sun,&nbsp;Anbing Zhang,&nbsp;Zhuo Zhou,&nbsp;Xing Liu","doi":"10.1016/j.virs.2026.07.009","DOIUrl":"10.1016/j.virs.2026.07.009","url":null,"abstract":"<div><div>Monkeypox virus (MPXV), a pathogenic orthopoxvirus, has caused major outbreaks and emerged as a global public health threat. Although antivirals approved for smallpox are used therapeutically against monkeypox, their clinical utility is limited by drug availability and emerging resistance. The conserved strategy by which viruses remodel host nucleotide metabolism to secure biosynthetic precursors for replication and spread has emerged as a pivotal target for the development of broad-spectrum antiviral therapeutics. In this study, leveraging the high genetic and biological similarity between vaccinia virus (VACV) and MPXV, we employed VACV as a surrogate model to screen 10 FDA-approved inhibitors targeting nucleotide metabolism enzymes, aiming to identify potential novel inhibitors against MPXV. Mycophenolate mofetil (MMF), an inosine 5′-monophosphate dehydrogenase type II (IMPDH2) inhibitor, displayed potent inhibition effects against both VACV and MPXV. Subsequent downstream time-course studies revealed that MMF targets a post-entry stage of the viral replication cycle. Mechanistic studies suggest that MMF inhibits IMPDH2 activity by suppressing ubiquitin-specific protease 5 (USP5)-mediated deubiquitination of IMPDH2 and inducing rod-and-ring (R&amp;R) assembly, leading to reducing dNTP pools and enhancing antiviral effects. In conclusion, our findings demonstrate that MMF is an effective antiviral drug against VACV and MPXV infection and establish a host-directed therapeutic strategy to combat future orthopoxvirus outbreaks.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 923-936"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A modular APEX biosensor enables sensitive and visualized monitoring of viral protease activity","authors":"Biao Li,&nbsp;Bao Dong,&nbsp;Yuehong Chen,&nbsp;Jing Li,&nbsp;Xiaoping Kang,&nbsp;Yuchang Li,&nbsp;Sen Zhang,&nbsp;Jiaqi Xiong,&nbsp;Zhengwei Zhang,&nbsp;Jun Hu,&nbsp;Shuimeng Song,&nbsp;Shenghai Huang,&nbsp;Ye Feng,&nbsp;Tao Jiang","doi":"10.1016/j.virs.2026.08.001","DOIUrl":"10.1016/j.virs.2026.08.001","url":null,"abstract":"<div><div>Viral proteases are key targets for the development of broad-spectrum antiviral drugs development. However, screening platform capable of accurately assessing inhibitor activity within physiologically relevant cellular environments remain urgently needed. Traditional methods, such as fluorescent protein assays and Förster resonance energy transfer (FRET), suffer from significant limitations, including susceptibility to non-specific conformational interference by test compounds and an inability to faithfully reflect intracellular inhibitory effects. To address these challenges, we constructed two modular biosensors (TS3AR and C3SIR) based on engineered ascorbate peroxidase (APEX). Their detection mechanism relies on specific cleavage of the substrate recognition sequence by the target protease, which triggers the reassembly of split APEX fragments, restores enzymatic activity, and generates fluorescent signals generated via cascade amplification reaction. Validation using the coronavirus main protease (Mpro) as a model showed that the TS3AR sensor achieved the signal-to-noise ratio up to 1500-fold for enzyme activity detection, while the C3SIR sensor effectively avoided the false positives caused by conformational interference seen in traditional methods and accurately identified high-potency Mpro inhibitors, including enstrelvir, PF-00835231, and nirmatrelvir. Moreover, by replacing the protease recognition sequence, these modular biosensors can be flexibly adapted for activity analysis and drug evaluation of Mpro from various coronaviruses (e.g., SARS-CoV-2, MERS-CoV) as well as other viral proteases (e.g., enterovirus 71, Epstein-Barr virus and hepatitis A virus). Overall, this platform provides a reliable, highly specific intracellular screening tool to accelerate the development of broad-spectrum therapeutics against both emerging and existing viral threats.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 972-987"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The antiviral role of TRIM25 in mammalian embryonic stem cells","authors":"Jie Zou,&nbsp;Yuxin Lin,&nbsp;Chunyan Wu,&nbsp;Yao Ji,&nbsp;Xuankai Zhao,&nbsp;Zhan Xu,&nbsp;Jingfei Gong,&nbsp;Zhiyuan Shi,&nbsp;Tianyang Luo,&nbsp;Xiaoling Xie,&nbsp;Yanan Jiang,&nbsp;Qi Tian,&nbsp;Shuqi Zhang,&nbsp;Yanxi Ji,&nbsp;Yuan Li,&nbsp;Zhenyu He,&nbsp;Shuchun Zhang,&nbsp;Liu Cao,&nbsp;Chun-Mei Li,&nbsp;Junyu Wu,&nbsp;Deyin Guo","doi":"10.1016/j.virs.2026.07.011","DOIUrl":"10.1016/j.virs.2026.07.011","url":null,"abstract":"<div><div>Mammalian embryonic stem cells (ESCs), despite lacking functional interferon (IFN) signaling, are remarkably resistant to viral infection. However, the mechanistic basis of their antiviral defenses remains incompletely characterized. In this study, we investigated the antiviral functional role and molecular mechanism of tripartite motif-containing protein 25 (TRIM25), a well-known key driver of IFN-dependent innate immunity, in IFN-deficient mouse ESCs (mESCs). TRIM25 exhibited a broad spectrum of antiviral activity in mESCs. RNAi depletion or CRISPR-mediated knockout of TRIM25 markedly enhanced the replication and propagation of both encephalomyocarditis virus (EMCV) and vesicular stomatitis virus (VSV). Mechanistically, the antiviral activity of TRIM25 in mESCs is independent of both IFN production and constitutive ISG expression. In virus-infected mESCs, TRIM25 translocated from the nucleus to the cytoplasm and directly bound viral RNA, where it formed cytoplasmic condensates with GTPase-activating protein-binding protein 1 (G3BP1) that colocalized with dsRNA foci. Genetic perturbation of G3BP1 similarly compromised the antiviral defenses of mESCs, revealing an essential synergism between TRIM25 and stress granule components in restricting viral replication. Our study identifies TRIM25 as a pivotal RNA-sensing effector in ESCs, delineating a previously unrecognized IFN-independent axis of intrinsic immunity that bridges viral RNA surveillance with stress granule-mediated suppression, thereby expanding the paradigm of pluripotent cell-autonomous antiviral strategies.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 820-831"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pygenic acid A, a small-molecule PD-1/SHP-2 inhibitor, enhances efficacy of therapeutic melanoma vaccines and prophylactic influenza vaccines","authors":"Yan Yan,&nbsp;Yitong Li,&nbsp;Wenyi Mei,&nbsp;Yixin Li,&nbsp;Qian Wang,&nbsp;Honglin Li,&nbsp;Lu Lu,&nbsp;Shibo Jiang","doi":"10.1016/j.virs.2026.07.006","DOIUrl":"10.1016/j.virs.2026.07.006","url":null,"abstract":"<div><div>Overcoming immunosuppressive tumor microenvironments remains a critical challenge in advanced vaccine development. Here, we evaluated Pygenic acid A (PA), an intracellular small-molecule inhibitor targeting the PD-1/SHP-2 axis, as a novel vaccine adjuvant. The adjuvant efficacy of PA was systematically assessed in two murine models: a therapeutic B16-F10 melanoma lung metastasis model and a prophylactic lethal H1N1 influenza virus challenge model. In the melanoma metastasis model, PA potentiated the anti-tumor effect of the mTRP2 vaccine, markedly inhibiting pulmonary metastatic lesions and prolonging the survival of tumor-bearing mice. Mechanistically, PA robustly boosted the intratumoral infiltration of functional T cells, thereby reversing local tumor immunosuppression. In the influenza vaccination model, consistent immunostimulatory effects were observed: the PA-adjuvanted hemagglutinin (HA) vaccine effectively elicited broad-spectrum cross-neutralizing antibody responses and provided complete protection against lethal heterologous influenza virus challenge. Further mechanistic investigations demonstrated that PA specifically promoted the differentiation of T follicular helper (Tfh) cells and the expansion of germinal center (GC) B cells in draining lymph nodes, while triggering a robust Th1-type cellular immune response dominated by IFN-γ secretion. Furthermore, <em>in vivo</em> safety assessments verified that PA intervention induced no obvious systemic inflammation, hematological abnormalities, or visceral organ injury, indicating a favorable safety profile. Collectively, these results demonstrate that PA serves as a potent and safe intracellular checkpoint-targeting adjuvant capable of potentiating both cellular immunity and cross-protective humoral immunity, holding great translational promise for the development of advanced cancer vaccines and broad-spectrum influenza vaccines.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 961-971"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 3CLpro inhibits the replication of influenza viruses through the cleavage of NP and PA","authors":"Liubing Du,&nbsp;Xiaoyu Cai,&nbsp;Ziliang Peng,&nbsp;Mengxuan Wang,&nbsp;Huijie Li,&nbsp;Xue Liu,&nbsp;Zhihui Zhang,&nbsp;Manqi Cao,&nbsp;Shuchun Zhang,&nbsp;Zhenyu He,&nbsp;Zhanjia Zhang,&nbsp;Yu Yan,&nbsp;Qitong Lin,&nbsp;Yushan Xue,&nbsp;Deyin Guo,&nbsp;Ji-An Pan,&nbsp;Yao-Qing Chen,&nbsp;Xiaoxue Peng","doi":"10.1016/j.virs.2026.08.006","DOIUrl":"10.1016/j.virs.2026.08.006","url":null,"abstract":"<div><div>The co-circulation of multiple viruses can lead to distinct pathological outcomes, yet how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection influences other viral infections remains poorly understood, despite its documented high frequency during the pandemic. In this study, we investigated how the proteolytic activity of SARS-CoV-2 3C-like protease (3CLpro) influences the replication of influenza A virus. <em>In silico</em> analysis identified candidate 3CLpro cleavage sites across numerous viral proteins, and biochemical assays confirmed that 3CLpro catalyzes the degradation of influenza virus nucleoprotein (NP) and polymerase acidic protein (PA) in a manner requiring its protease activity. This degradation of NP and PA, which are essential for viral genome packaging and transcription, disrupted the influenza replicative cycle and suppressed viral replication, both upon ectopic 3CLpro expression and during SARS-CoV-2 infection. Our data uncover a direct, enzyme-based mechanism by which SARS-CoV-2 can suppress influenza virus replication during coinfection. We provide a molecular explanation for the sharp, global decline in influenza activity observed during the COVID-19 pandemic and illustrate how enzymatic weapons of one virus can be repurposed to restrain a competing pathogen.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 842-854"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enteroviruses antagonize the host restriction factor ABL2 via proteasomal degradation to facilitate viral replication","authors":"Mengran Yuan,&nbsp;Xiaorong Qiao,&nbsp;Hua Wang,&nbsp;Nuo Chen,&nbsp;Yan Wang,&nbsp;Yuhan Li,&nbsp;Xiaoxiang Zhou,&nbsp;Zengjun Ji,&nbsp;Hongxing Shen","doi":"10.1016/j.virs.2026.08.003","DOIUrl":"10.1016/j.virs.2026.08.003","url":null,"abstract":"<div><div>Enteroviruses, including Coxsackievirus B3 (CVB3), are significant human pathogens that cause severe diseases, such as viral myocarditis, pancreatitis, and encephalitis. <em>ABL</em> proto-oncogene 2 (ABL2), a non-receptor tyrosine-protein kinase, regulates diverse physiological processes and participates in virus infection; however, its role in enterovirus infection remains uncharacterized. Here, we demonstrate a novel host-virus interaction: enteroviruses degrade ABL2 via the ubiquitin-proteasome system through their non-structural protein 2B. Furthermore, ABL2 functions as an antiviral restriction factor during enterovirus infection, specifically inhibiting the early stages of viral replication. Mechanistically, ABL2 directly interacts with RAC1, a Rho family GTPase, and downregulates RAC1 protein levels, thereby suppressing RAC1-dependent activation of the PI3K/AKT signaling pathway. In summary, our study reveals a post-translational mechanism by which enteroviruses evade host antiviral defenses, providing a rationale for therapeutic development against enteroviral diseases.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 855-867"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hijacking the host heparan sulfate-cell-surface ribonucleoproteins (RNPs) scaffold pathway for viral immune evasion","authors":"Wei Ye,&nbsp;Yangchao Dong,&nbsp;He Liu,&nbsp;Hongwei Ma,&nbsp;Yingfeng Lei,&nbsp;Fanglin Zhang","doi":"10.1016/j.virs.2026.06.006","DOIUrl":"10.1016/j.virs.2026.06.006","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 999-1001"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148219713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}