{"title":"A HiBiT-Tagged Influenza A Virus Reporter System Reveals Cytokine-Inhibitory Micropeptide 53 as a Modulator of Viral Infection and Immunopathology.","authors":"Shujie Ma, Sha Liu, Conghui Zhao, Wenjun Shi, Chunping Zhang, Jiacheng Huang, Yang Wang, Xiaoxuan Zhang, Haoxi Qiang, Huanhuan Wang, Peilin Li, Xinhui Chen, Ziyi Zhang","doi":"10.1016/j.virs.2026.09.003","DOIUrl":"https://doi.org/10.1016/j.virs.2026.09.003","url":null,"abstract":"<p><p>Influenza A virus (IAV) remains a major threat to human and animal health, highlighting the need for efficient approaches to identify host factors and antivirals. Reporter viruses are critical tools for these efforts, but incorporating large reporter genes often compromises viral fitness and genetic stability. Here, we developed a replication competent reporter IAV by fusing an 11-amino acid HiBiT tag into the nonstructural protein 1 (NS1) of the A/WSN/1933 (H1N1) backbone. The modified virus retained parental virion morphology, comparable replication kinetics, and in vivo tissue tropism, while enabling the highly sensitive, rapid, and quantitative detection of viral replication. Using this reporter virus, we established a robust high-throughput screening (HTS) platform with excellent assay quality and validated its capability to identify host regulators of IAV infection. Application of this platform to host-encoded micropeptides (miPEPs) led to the identification of cytokine-inhibitory micropeptide 53 (CIM53) as a novel regulator of IAV replication. Mechanistically, CIM53 promoted IAV replication by intrinsically suppressing antiviral innate immune responses. Furthermore, although CIM53 enhanced viral replication, its immunomodulatory activity contributed to reduced lung injury and improved survival when combined with Oseltamivir (OSV) treatment in infected mice. Our study establishes a highly practical screening platform for virological research and highlights CIM53 as a potential host-directed adjunct therapy for severe IAV Infection.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897978","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}
Virologica SinicaPub Date : 2026-09-04DOI: 10.1016/j.virs.2026.09.002
Qiong Mo, Yun-Jia Ning
{"title":"ACSL3 at the UPR crossroads: Tactician of anti-influenza defense, target of influenza offense.","authors":"Qiong Mo, Yun-Jia Ning","doi":"10.1016/j.virs.2026.09.002","DOIUrl":"https://doi.org/10.1016/j.virs.2026.09.002","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892477","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}
Virologica SinicaPub Date : 2026-09-02DOI: 10.1016/j.virs.2026.08.016
Lin Jiang, Xinhong Tian, Keran Ma, Wentao Qiao, Juan Tan
{"title":"RNF152 regulates prototype foamy virus replication by targeting Gag polyubiquitination and VLPs production.","authors":"Lin Jiang, Xinhong Tian, Keran Ma, Wentao Qiao, Juan Tan","doi":"10.1016/j.virs.2026.08.016","DOIUrl":"https://doi.org/10.1016/j.virs.2026.08.016","url":null,"abstract":"<p><p>Prototype foamy viruses (PFVs) are complex retroviruses that establish long-term latent infections in hosts without causing disease, positioning them as potential safe gene transfer vectors. Understanding the host proteins involved in PFV replication and their interaction mechanisms may enhance gene transfer efficiency. However, only a few cellular proteins are known to influence PFV replication. Based on the transcriptomic analysis of PFV-infected HT1080 cells, we observed a potential significance of RING finger protein 152 (RNF152) in modulating PFV replication. Overexpression of RNF152 significantly inhibits PFV replication, whereas RNF152 knockdown enhances viral replication. Mechanistically, RNF152 interacts with the Gag protein to promote its polyubiquitination at lysine 396 (K396), thereby facilitating its degradation via the ubiquitin-proteasome system. Furthermore, RNF152 reduces the size and number of PFV virus-like particles (VLPs) by inhibiting the multimerization of Gag. Collectively, our findings reveal a previously unrecognized mechanism that influences PFV infection. Additionally, we elucidate the role of RNF152 in affecting virus replication for the first time, providing valuable insights into the mechanisms of virus replication and demonstrating the importance of ubiquitination modification in affecting viral replication.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881362","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":"Liver injury during Ebola virus infections: Characteristics and molecular mechanisms.","authors":"Shuai Sui, Kaiyue Zhang, Xiaofan Shen, Xia Chuai, Sandra Chiu","doi":"10.1016/j.virs.2026.08.015","DOIUrl":"https://doi.org/10.1016/j.virs.2026.08.015","url":null,"abstract":"<p><p>Ebola virus (EBOV) causes severe and often fatal Ebola virus disease (EVD) in humans, posing a major threat to global public health. Since EVD was first identified in the Democratic Republic of Congo (DRC) in 1976, the World Health Organization (WHO) has declared it a Public Health Emergency of International Concern (PHEIC) on three occasions. EBOV infection is characterized by rapid progression from non-specific febrile illness to severe gastrointestinal symptoms, followed by hemorrhagic fever and multi-organ dysfunction, with case fatality rates reaching as high as 90%. The liver is a primary target of EBOV, and virus-induced liver injury is characterized by elevated aspartate aminotransferase (AST) levels, mild hyperbilirubinemia, impaired coagulation factor synthesis, hepatocyte necrosis, and robust inflammatory responses, all of which are closely correlated with disease severity and mortality risk. In this review, we summarize the characteristics and mechanisms of EBOV-induced liver injury, which may help to further elucidate the pathogenesis of EVD and provide novel strategies for combating EBOV infection.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841029","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}
Virologica SinicaPub Date : 2026-08-26DOI: 10.1016/j.virs.2026.08.014
Mingyue Song, Shuyi Wang, Xiao Fei, Guijie Guo
{"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":"https://doi.org/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 cccDNA 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}
Virologica SinicaPub Date : 2026-08-26DOI: 10.1016/j.virs.2026.08.012
Bo Yang, Zhi-Yu Liu, Feng Xiong, Han Cheng, Min-Hua Luo, Wen-Bo Zeng
{"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}
Virologica SinicaPub Date : 2026-08-24DOI: 10.1016/j.virs.2026.08.013
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
{"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":"https://doi.org/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}
Virologica SinicaPub Date : 2026-08-22DOI: 10.1016/j.virs.2026.08.011
Aofan Wang, Jiale Li, Lin Chen, Baoyin Su, Jiapei Han, Ke Zhang, Yuxin Chen
{"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":"https://doi.org/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, m<sup>6</sup>A-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 m<sup>6</sup>A 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}
Virologica SinicaPub Date : 2026-08-11DOI: 10.1016/j.virs.2026.08.009
Yu Guo, Meijing Hong, Xuefei Sun, Yuhang Liu, Yue Sun, Le Yi, Biao He, Guoqiang Zhu, Zhongzhong Tu, Changchun Tu
{"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, Guoqiang Zhu, Zhongzhong Tu, Changchun Tu","doi":"10.1016/j.virs.2026.08.009","DOIUrl":"https://doi.org/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}