Virologica Sinica最新文献

{"title":"Viral manipulation of DNA damage response signaling: Molecular mechanisms and therapeutic implications.","authors":"Mingyue Song, Shuyi Wang, Xiao Fei, Guijie Guo","doi":"10.1016/j.virs.2026.08.014","DOIUrl":"10.1016/j.virs.2026.08.014","url":null,"abstract":"<p><p>The DNA damage response (DDR) network maintains genomic integrity, functions as a signaling hub that viruses exploit to drive pathogenesis, and constitutes a central interface between viral infection and host cell fate. This review discusses the molecular mechanisms by which viruses subvert host DDR pathways, with an emphasis on viral replication, latency, immune evasion, and host genomic instability. Representative examples include PARP1-dependent ccDNA stabilization by hepatitis B virus (HBV), MRN complex sequestration by herpes simplex virus type 1 (HSV-1) for immune evasion, ATM signaling modulation by human immunodeficiency virus (HIV) to maintain viral latency, and DDR activation triggered by RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus (ZIKV), and influenza A virus (IAV) via oxidative stress. We evaluate emerging DDR-targeted antiviral strategies, including restoring intrinsic host restriction, exploiting synthetic lethality of dysregulated DDR kinases, and therapeutically modulating DDR-innate immune crosstalk to restore antiviral surveillance (e.g., by stabilizing MRE11 or inhibiting PARP7). Bridging molecular insights with clinical translation, this review positions DDR targeting as a mechanism-driven, host-directed antiviral paradigm.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148832811","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":"Engineering HSV-1 for Gene Therapy, Oncolytic Immunotherapy, and Neuroscience.","authors":"Bo Yang, Zhi-Yu Liu, Feng Xiong, Han Cheng, Min-Hua Luo, Wen-Bo Zeng","doi":"10.1016/j.virs.2026.08.012","DOIUrl":"https://doi.org/10.1016/j.virs.2026.08.012","url":null,"abstract":"<p><p>Herpes simplex virus type 1 (HSV-1) has emerged as a versatile platform for gene delivery, oncolytic immunotherapy, and neural circuit mapping. Its large genome, broad tropism, and engineering flexibility enable delivery of large or multi-component payloads that exceed the capacity of many conventional viral vectors. HSV-1-based vectors span a continuum of architectures, each representing a distinct design space shaped by trade-offs among replication competence, payload size, immune engagement, biosafety, and manufacturing robustness. Advances in bacterial artificial chromosome recombineering, CRISPR-based editing, and synthetic genome assembly, together with insights from structural and systemic biology, have accelerated the transition from empirical vector construction to more rational programmable genome design. These technologies enable modular control of viral entry, transcription, genome replication/maintenance, and host immune interactions. Clinical successes such as T-VEC, G47Δ, and B-VEC have validated the clinical potential of HSV-1 engineering, yet broader translation remains limited by antiviral immunity, inefficient delivery, epigenetic silencing, genome instability, and manufacturing challenges. In this review, we illustrate how HSV-1 has evolved from a naturally neurotropic virus into a versatile biomedical tool, whose therapeutic and research potential emerges from the precise matching of viral properties with disease-specific requirements, delivery contexts, and functional objectives.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148832826","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 fatal human case of co-infection with severe fever with thrombocytopenia syndrome virus and Nairobi sheep disease virus.","authors":"Liyan Fu, Hongzhi Xu, Ying Peng, Chenxuan Li, Jun Ni, Yanfang Zhang, Xijia Liu, Jie Fu, Zhengyuan Su, Jin Qian, Jiayin Jin, Jinfeng Xiong, Qi Chen, Xuhua Guan, Shuang Tang, Fei Deng, Dan Liu, Shu Shen, Banghua Chen, Xiaoli Wu","doi":"10.1016/j.virs.2026.08.013","DOIUrl":"10.1016/j.virs.2026.08.013","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814321","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":"RNA-centered regulation in SFTSV infection: Mechanisms, host interactions, and translational implications.","authors":"Aofan Wang, Jiale Li, Lin Chen, Baoyin Su, Jiapei Han, Ke Zhang, Yuxin Chen","doi":"10.1016/j.virs.2026.08.011","DOIUrl":"10.1016/j.virs.2026.08.011","url":null,"abstract":"<p><p>Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen that causes substantial morbidity and high case fatality in severe cases, representing a major public health concern in East Asia. Although protein-mediated mechanisms of SFTSV replication and immune evasion have been extensively studied, accumulating evidence indicates that viral infection is also influenced by RNA-centered regulatory processes. These processes include viral RNA transcription and replication, epitranscriptomic modification, host RNA-binding proteins, RNA interference-related pathways, small RNA responses, and NSs-driven inclusion bodies. Current evidence is strongest for L protein-mediated viral RNA transcription and replication, m⁶A-related regulation of viral RNA stability and translation, selected host RNA-binding proteins involved in viral RNA metabolism, and NSs-mediated antagonism of AGO2-dependent RNA interference and antiviral signaling. In contrast, the direct role of m⁶A in innate immune sensing, the functional significance of virus-derived microRNA-like small RNAs, and the physical protection of viral RNA within NSs-driven condensates remain incompletely established. In this review, we summarize current knowledge of how RNA-centered mechanisms regulate SFTSV RNA fate, viral replication, host adaptation, immune antagonism, and cross-host transmission. We further discuss their potential implications for biomarker discovery and antiviral development, while emphasizing the uneven strength of evidence and the mechanistic and translational barriers that remain. An evidence-stratified RNA-centered framework may help prioritize future studies and guide the rational exploration of RNA-based diagnostic and therapeutic strategies for SFTSV infection.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798348","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":"First insight into the virome composition of the vulnerable Naemorhedus griseus.","authors":"Yu Guo, Meijing Hong, Xuefei Sun, Yuhang Liu, Yue Sun, Le Yi, Biao He, Changchun Tu, Guoqiang Zhu, Zhongzhong Tu","doi":"10.1016/j.virs.2026.08.009","DOIUrl":"10.1016/j.virs.2026.08.009","url":null,"abstract":"<p><p>The Chinese goral (Naemorhedus griseus) is identified as a vulnerable species on the Red List of China's Biodiversity and listed as a national second-class key protected wild animal in China. Despite its widespread distribution in China, there has been scant research into the pathogens harbored by this species, and our understanding of the virus diversity remains limited. In the present study, we performed the whole virome profiling of a rescue-failed Naemorhedus griseus, which identified a diverse viral community across multiple organ tissues of the animal. Specifically, abundant bacteriophages, several plant-derived viruses, and multiple mammalian viruses, i.e., two distinct parvoviruses, novel picobirnaviruses, and a novel phenuivirus. Additionally, virus-carrier determination analysis that Naemorhedus griseus-borne viruses are related to plants, mammals, and arthropods. These data provide the first insight into the genetic diversity of Naemorhedus griseus-borne viruses, and their transmission dynamics across humans, domestic animals, arthropods, and wildlife. This study not only expands the existing repertoire of viral genomic information and delineates the host range of these pathogens but also underscores the imperative of implementing a One Health strategy for the surveillance and control of wildlife-borne viral pathogens.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713679","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":"Ferritin nanoparticle-based vaccine enhances mucosal immunity by promoting antigen uptake and activation of alveolar macrophages.","authors":"Xiantao Zhang, Yingtong Lin, Jie Liu, Dongming Wang, Jiayi Yuan, Ran Chen, Xu Zhang, Xue Zhang, Nan Zhou, Hui Zhang, Xin He","doi":"10.1016/j.virs.2026.08.004","DOIUrl":"10.1016/j.virs.2026.08.004","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707826","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":"The C-terminal T234 residue of VP3 is required for KREMEN1 receptor-dependent infectivity and pathogenesis of coxsackieviruses A10 and A8","authors":"Xingyu Yan,&nbsp;Zeyu Liu,&nbsp;Kexin Liu,&nbsp;Zhenlin Yang,&nbsp;Jianxing Wang,&nbsp;Chao Zhang","doi":"10.1016/j.virs.2026.07.002","DOIUrl":"10.1016/j.virs.2026.07.002","url":null,"abstract":"<div><div>Coxsackievirus A10 (CVA10) is a major causative agent of hand, foot and mouth disease and utilizes KREMEN1 (KRM1) as its cellular receptor. While our previous work identifies VP2 residue K140 as a universal anchor for KRM1 binding among KRM1-utilizing enteroviruses, the functional significance of other receptor-interface residues remains poorly characterized. Here, through structure-guided mutagenesis, we demonstrate that VP3-T234, a completely conserved residue at the C-terminus of VP3, is essential for CVA10 infectivity. The T234A mutation does not affect virion assembly but abolishes both KRM1 binding and cellular attachment. Interestingly, this requirement shows remarkable virus specificity: the homologous residue is critical for CVA8, but is not required for other KRM1-utilizing enteroviruses including CVA2–CVA6 and CVA12. The T234A mutation significantly attenuates the pathogenesis of both CVA10 and CVA8 in neonatal mice. Moreover, the CVA8-T234A mutant provides complete protection as an attenuated vaccine against lethal CVA8 challenge. Our findings establish a model wherein KRM1 engagement relies on the conserved VP2-K140 anchor complemented by virus-specific secondary residues, with VP3-T234 representing a key determinant for CVA10 and CVA8. These insights advance our understanding of enterovirus-receptor interactions and provide new directions for vaccine development.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 882-897"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148413125","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":"Identification and characterization of anti-chikungunya virus compounds using a biosafe toolkit","authors":"Yang Gao,&nbsp;Guojie Wang,&nbsp;Hanhua Zhang,&nbsp;Sicheng Tian,&nbsp;Yanqun Wang,&nbsp;Jincun Zhao,&nbsp;Xing Liu,&nbsp;Rong Ye,&nbsp;Rong Zhang","doi":"10.1016/j.virs.2026.08.005","DOIUrl":"10.1016/j.virs.2026.08.005","url":null,"abstract":"<div><div>Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus for which no specific antiviral therapy is currently available. During the large outbreak in Foshan, Guangdong Province, China, in July 2025, CHIKV rapidly spread to neighboring regions and caused more than 16,000 confirmed cases. In this study, the predominant outbreak strain of CHIKV was selected as the reference sequence to establish a panel of complementary biosafe tools for antiviral compound screening and mechanistic investigation. A virus replicon particle (VRP) system for CHIKV was first constructed and applied to compound library screening, resulting in the identification of three candidate antiviral compounds: MDL-12330A, bazedoxifene acetate, and anidulafungin. To further validate their antiviral activities and investigate their potential mechanisms, CHIKV functional evaluation systems were subsequently established, including vesicular stomatitis virus (VSV)- and murine leukemia virus (MLV)-based pseudovirus systems for viral entry, a replicon RNA system for post-entry replication-associated processes, a replication-defective nsP4 mutant replicon RNA system for primary translation, and a virus-like particle (VLP) system for viral particle assembly and budding assessment. Using these complementary systems, we systematically evaluated the antiviral profiles of the three candidate compounds across multiple stages of the CHIKV life cycle. This analysis revealed distinct stage-specific inhibitory patterns and provided insights into their potential antiviral mechanisms, which warrant validation using authentic CHIKV infection to assess their translational potential.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 779-790"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707822","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":"Genetic heterogeneity and pathogenic potential of historical Crimean-Congo hemorrhagic fever virus isolates in China","authors":"Abulimiti Moming,&nbsp;Yuan Bai,&nbsp;Qiong Zhu,&nbsp;Jiayin Jin,&nbsp;Yaohui Fang,&nbsp;Shouwei Huang,&nbsp;Qiaoli Wu,&nbsp;Zhengyuan Su,&nbsp;Guoyu Zhao,&nbsp;Shuang Tang,&nbsp;Manli Wang,&nbsp;Zhihong Hu,&nbsp;Yujiang Zhang,&nbsp;Fei Deng,&nbsp;Shu Shen","doi":"10.1016/j.virs.2026.07.012","DOIUrl":"10.1016/j.virs.2026.07.012","url":null,"abstract":"<div><div>The Crimean-Congo hemorrhagic fever virus (CCHFV) poses a significant public health threat. In China, CCHFV has been circulating for decades, yet the genomic diversity and pathogenic potential of the circulating strains remain poorly characterized, hindering risk assessment and countermeasure development. In this study, we recovered 24 historical CCHFV strains isolated between 1966 and 2004 from humans, ticks and jerboas in Xinjiang Uyghur Autonomous Region of China. Whole-genome sequencing was performed, followed by comprehensive analyses of their phylogenetic relationships, <em>in vitro</em> infectivity and <em>in vivo</em> pathogenicity. Phylogenetic analyses revealed high genetic heterogeneity, identifying seven genotypes for the L segment, nine for the M segment (including a novel Asia 4 genotype), and nine for the S segment. Amino acid mutation analysis revealed that the mucin-like domain (MLD) of the glycoprotein (GP) exhibited the highest mutation rate, contributing substantially to sequence diversity. <em>In vitro</em>, Asia 2 (75024) and Asia 3 (79121M18) strains exhibited robust replication in monkey-, hamster-, and human-derived cell lines. In C57BL/6 mice, all four representative strains induced viral replication and specific antibody responses (IgM and IgG), causing mild to moderate pathological damage in the liver, spleen, and kidneys. In IFNAR^−/− mice, virulence varied markedly among representative strains: Asia 2 and Asia 3 strains were highly lethal (LD₅₀ &lt; 1 TCID₅₀), Asia 1 was moderately virulent (LD₅₀ = 142.5 TCID₅₀), and Asia 4 exhibited atypical, non-dose-dependent mortality. Collectively, our work reports a novel Asia 4 genotype and suggests strain- and lineage-associated differences in virulence for CCHFV in China, providing critical insights for surveillance and targeted countermeasure development.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 832-841"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649072","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":"Recent progress in anti-Chikungunya virus drug discovery: Focus on the viral life cycle and direct-acting antivirals","authors":"Chunjiao Liu,&nbsp;Shixiang Pan,&nbsp;Mingxue Gao,&nbsp;Yumin Zhang,&nbsp;Leike Zhang,&nbsp;Bin Lin,&nbsp;Xiangrui Jiang","doi":"10.1016/j.virs.2026.07.001","DOIUrl":"10.1016/j.virs.2026.07.001","url":null,"abstract":"<div><div>Chikungunya virus (CHIKV) belongs to the genus <em>Alphavirus</em> of the family <em>Togaviridae</em>. CHIKV infection generally causes severe clinical symptoms, including debilitating arthralgia, fever, hemorrhage and cutaneous rashes. In recent years, the transmission range of CHIKV has continued to expand, resulting in recurrent local outbreaks in densely populated and economically developed regions and posing a severe threat to public health. Accordingly, safe and effective anti-CHIKV therapeutics are urgently needed for the clinical treatment of infected patients. Nevertheless, no specific anti-CHIKV drugs have been approved for clinical use or advanced into clinical trials, and relevant research and development remain confined to the preclinical stage. This review systematically illustrates the key steps of the CHIKV life cycle, core viral components and vital functional domains, and summarizes the current research progress of anti-CHIKV agents. It comprehensively outlines the discovery strategies, structural optimization directions and activity evaluation approaches of anti-CHIKV small-molecule compounds, and further investigates their action targets. Notably, nsP2 and nsP4 represent promising targets for broad-spectrum anti-CHIKV even anti-alphavirus drug development due to their structural conservation across alphavirus species and druggable features. This work provides a solid theoretical basis and valuable reference for the future research and development of novel anti-CHIKV drugs.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 735-752"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397961","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}