{"title":"Degradation of ACSL3 by influenza A virus shifts unfolded protein response from antiviral defense to viral evasion","authors":"Shuoxuan Zhao, Yichao Chen, Tianxin Zhang, Yaoyao Gao, Jing Wu, Fangji Yang, Yongxiang Liu, Xuesong Liu, Nan Qi","doi":"10.1016/j.virs.2026.06.008","DOIUrl":"10.1016/j.virs.2026.06.008","url":null,"abstract":"<div><div>Host restriction factors and viral evasion strategies involved in the virus-host arms races remain to be discovered. Through an initial membrane protein-targeted CRISPR-Cas9 screening, we identified Acyl-CoA synthetase long-chain family member 3 (ACSL3) as a restriction factor against influenza A virus (IAV). Clinical transcriptomic analysis shows that ACSL3 is upregulated in peripheral blood mononuclear cells from mildly ill patients with influenza. Ectopic expression and loss-of-function validation demonstrate the physiological role of ACSL3 in restricting viral proliferation of diverse IAV subtypes (H1N1, H3N2, H3N8) <em>in vitro</em> and <em>in vivo</em>. Mechanistically, ACSL3 potentiates the antiviral unfolded protein response (UPR) by engaging the endoplasmic reticulum (ER) stress sensors IRE1α and PERK, thereby enhancing the IRE1α-XBP1-s driven inflammation and inhibiting the PERK-ATF4-CHOP mediated apoptosis. Conversely, IAV triggers the lysosomal degradation of ACSL3 and thus reprograms UPR to promote an immunologically silent apoptosis for viral egress and dissemination. Our findings establish ACSL3 as a molecular switch balancing the UPR-mediated antiviral response, and reveal a targeted viral evasion strategy in the virus-host interplay.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 3","pages":"Pages 638-650"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253576","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}
Virologica SinicaPub Date : 2026-06-01Epub Date: 2026-05-14DOI: 10.1016/j.virs.2026.05.002
Ying Li, Jingyuan Zhang, Haizhou Liu, Muhammad Noman, Muhammad Arif Rizwan, Ismaila Damilare Isiaka, Hebin Chen, Wenqing Li, Nan Zhao, Yan Li, Yamin Sun, Xiaoxia Lu, Di Liu, Yi Yan
{"title":"Age-related pharyngeal microbiome and host transcriptomic signatures underlying fever responses in RSV bronchiolitis","authors":"Ying Li, Jingyuan Zhang, Haizhou Liu, Muhammad Noman, Muhammad Arif Rizwan, Ismaila Damilare Isiaka, Hebin Chen, Wenqing Li, Nan Zhao, Yan Li, Yamin Sun, Xiaoxia Lu, Di Liu, Yi Yan","doi":"10.1016/j.virs.2026.05.002","DOIUrl":"10.1016/j.virs.2026.05.002","url":null,"abstract":"<div><div>Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of hospitalization in infancy and exhibits pronounced age-dependent clinical heterogeneity. Fever becomes increasingly prevalent with age, yet whether febrile representation reflects a uniform inflammatory and immune phenotype across infancy remains unclear. In this prospective cohort of infants hospitalized with RSV bronchiolitis, we performed an integrated analysis of clinical features, pharyngeal microbiome composition, host transcriptomic profiles, and host-microbe interaction networks, with particular attention to age-related variation in fever-associated patterns. Clinically, fever prevalence exhibited a strong age-dependent increase across infancy. Correspondingly, canonical correspondence analysis identified age and fever as dominant gradients related to variation in both pharyngeal microbiome composition and host gene expression. Although no significant age-dependent correlations were observed at the global microbial and host transcriptomic levels in the fever-age interaction model, distinct patterns of microbial and host responses related to fever were observed across different age groups. Specifically, ranked gene set enrichment analysis indicated that febrile infants in early infancy showed relative attenuation of host defense-related programs, whereas older infants showed stronger enrichment of antiviral and inflammatory effector pathways, with more selective regulatory and signaling-associated patterns in late infancy. Integrated host-microbe network analysis further delineated a coherent developmental trajectory of fever-associated interaction architectures, evolving from densely interconnected regulatory networks in early infancy to modular, selectively coupled, host-centered configurations with advancing age. Together, febrile responses in RSV bronchiolitis should not be interpreted as a uniform biological phenotype across infancy and support age-aware interpretation of fever in pediatric RSV infection.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 3","pages":"Pages 574-585"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147949757","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}
Virologica SinicaPub Date : 2026-06-01Epub Date: 2026-06-03DOI: 10.1016/j.virs.2026.05.009
Jiaxiang Li, Kewei Chen, Xin Chen, Kaiyang Zheng, Shujuan Sun, Hao Yu, Yue Dong, Ziyue Wang, Yixuan Xu, Andrew McMinn, Yeong Yik Sung, Wen Jye Mok, Li Lian Wong, Yantao Liang, Min Wang
{"title":"A comprehensive RNA virome from molluscan transcriptomes reveals extensive diversity and modular genome evolution","authors":"Jiaxiang Li, Kewei Chen, Xin Chen, Kaiyang Zheng, Shujuan Sun, Hao Yu, Yue Dong, Ziyue Wang, Yixuan Xu, Andrew McMinn, Yeong Yik Sung, Wen Jye Mok, Li Lian Wong, Yantao Liang, Min Wang","doi":"10.1016/j.virs.2026.05.009","DOIUrl":"10.1016/j.virs.2026.05.009","url":null,"abstract":"<div><div>Mollusca, the second-largest animal phylum, includes many aquaculture species used as important food resources for humans. While DNA viruses that threaten molluscan aquaculture have received much attention, molluscan RNA viromes are still understudied. Here, using a multi-stage RdRP discovery pipeline combining six-frame translation, profile-based homology search, and phylogenetic validation, 203 RNA viruses spanning five viral phyla and fifteen viral orders were identified, based on 223 molluscan metatranscriptomes covering eight classes. Phylogenetic analysis, combined with structural modeling, revealed a significant increase in the number of <em>Pisuviricota</em>-related lineages. Extensive modular evolution in viral genomes was observed, including gene rearrangements and co-evolution of capsid and RdRP genes. Host prediction linked 76% of the RNA viruses to a range of eukaryotes. These findings expand the diversity of RNA viruses associated with molluscs and shed light on their phylogenetic relationships, highlighting that molluscs might serve as an important reservoir of diverse RNA viruses infecting a range of eukaryotic hosts.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 3","pages":"Pages 532-542"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164789","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}
Virologica SinicaPub Date : 2026-06-01Epub Date: 2026-06-03DOI: 10.1016/j.virs.2026.05.011
Yi Wang, Fei Li, Hui Xu, Yiliang Fu, Guoshuang Feng, Hanwen Zhang, Juan Huang, Zhengde Xie, Xiangpeng Chen
{"title":"The epidemiology and disease burden of enterovirus infections among hospitalized children in China: An 8-year national cross-sectional study","authors":"Yi Wang, Fei Li, Hui Xu, Yiliang Fu, Guoshuang Feng, Hanwen Zhang, Juan Huang, Zhengde Xie, Xiangpeng Chen","doi":"10.1016/j.virs.2026.05.011","DOIUrl":"10.1016/j.virs.2026.05.011","url":null,"abstract":"<div><div>Enterovirus (EV) infections represent a significant global and national health concern in children, leading to various complications. Although most children with EV infections generally have a favorable prognosis, a small proportion may still develop severe complications. This study aimed to analyze the epidemiological characteristics, disease spectrum, and disease burden of EV infections in China. A total of 163,714 hospitalized children with EV infections from 37 member hospitals of the Futang Research Center of Pediatric Development were identified between Jan 1st, 2016 and Dec 31st, 2023, accounting for 1.49% of all pediatric hospitalizations. Most cases occurred in infants aged 28 days to ≤ 1 year (42.29%) and toddlers aged 1 to ≤ 3 years (39.93%), with a male predominance (male-to-female ratio, 1.62 : 1). Severe cases of EV infections can be life-threatening and increase the burden of disease. The median LOS for EV infections were 5 days, with an average hospitalization cost of $587.37. EV infections can affect multiple organs, including the heart, brain, and respiratory system and were associated with severe complications, including myocarditis, encephalitis, and meningitis. These findings underscore the substantial disease burden of EV infections and highlight the need for targeted prevention strategies in young children.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 3","pages":"Pages 513-522"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164840","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}
Virologica SinicaPub Date : 2026-06-01Epub Date: 2026-06-03DOI: 10.1016/j.virs.2026.06.001
Muhammad Ammar, Yaohui Fang, Muhammad Saqib, Jian Xiao, Awais-Ur-Rahman Sial, Qiaoli Wu, Muhammad Khalid Mansoor, Xiaoli Wu, Muhammad Moaaz, Muhammad Usama Butt, Rehman Hafeez, Kashif Iqbal, Ali Zohaib, Shu Shen, Fei Deng
{"title":"Metagenomic and serological evidence of emerging tick-borne viruses in livestock, humans, and rats in Pakistan","authors":"Muhammad Ammar, Yaohui Fang, Muhammad Saqib, Jian Xiao, Awais-Ur-Rahman Sial, Qiaoli Wu, Muhammad Khalid Mansoor, Xiaoli Wu, Muhammad Moaaz, Muhammad Usama Butt, Rehman Hafeez, Kashif Iqbal, Ali Zohaib, Shu Shen, Fei Deng","doi":"10.1016/j.virs.2026.06.001","DOIUrl":"10.1016/j.virs.2026.06.001","url":null,"abstract":"<div><div>Tick-borne viruses (TBVs) pose significant emerging threats to public and veterinary health worldwide. In Pakistan, the potential threats posed by TBVs extend far beyond Crimean-Congo hemorrhagic fever virus (CCHFV), which causes outbreaks and severe hemorrhaging with a high fatality rate among humans each year. However, the full extent of the tick-borne virome remains largely unexplored. This study presents the metagenomic profiling of viruses in livestock-associated ticks from Pakistan. Eighty-seven ticks belonging to the genera <em>Ixodes</em>, <em>Rhipicephalus</em>, <em>Haemaphysalis</em>, and <em>Hyalomma</em> species from livestock in Punjab. These ticks were subsequently grouped into 11 pools for RNA sequencing. Our analysis revealed extensive viral diversity, identifying sequences related to 31 viruses spanning at least 11 families. New strains of Jingmen tick virus (JMTV), Brown dog tick phlebovirus 2 (BDTPV-2), and Liman tick virus (LMTV) were characterized, confirming their presence in the region. Serological surveys performed among 319 livestock, 253 humans, and 214 rats detected antibodies against these viruses, indicating host exposure. Notably, the presence of JMTV-neutralizing antibodies was confirmed in two livestock animals, one human, and one rat, providing evidence of productive infection. Our findings significantly expand the known diversity and distribution of TBVs in Pakistan, establish the preliminary baseline of the tick virome in the country, and provide serological evidence of cross-species exposure to emerging TBVs. This study highlights the underestimated risk of tick-borne viral zoonoses in Pakistan and underscores the urgent need for enhanced surveillance and risk assessment.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 3","pages":"Pages 523-531"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164748","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":"Induction of mitochondrial fission and mtDNA leakage via the Smad3/Drp1 axis by PEDV infection activates the TLR9/NF-κB/IL-1β inflammatory pathway","authors":"Hangao Xie, Jinlian Guan, Fengjie Tian, Ting Xiong, Haixia Feng, Fei Xu, Ziqing Zhou, Dongsheng He, Dingxiang Liu, Ruiai Chen","doi":"10.1016/j.virs.2026.05.004","DOIUrl":"10.1016/j.virs.2026.05.004","url":null,"abstract":"<div><div>Mitochondrial homeostasis is intricately linked to the pathogenesis of many viral infections. The maintenance of mitochondrial homeostasis and normal cellular functions relies heavily on the delicate balance of mitochondrial dynamics. However, the precise impact of porcine epidemic diarrhea virus (PEDV) infection on mitochondrial dynamics and subsequent pathological processes is largely unexplored. In this study, through both <em>in vivo</em> and <em>in vitro</em> infections, we have demonstrated that PEDV infection induces mitochondrial fission and leakage of mtDNA by upregulating Drp1 expression, and identified Smad3 as a crucial transcription factor responsible for regulating Drp1 expression. By establishing an inflammatory model using PEDV-infected cells, we have identified Drp1-mediated mtDNA release as an upstream event triggering TLR9/NF-κB pathway activation during PEDV infection. These findings provide novel insights into the relationship between PEDV infection and host inflammatory responses from the perspective of mitochondrial dynamics.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 3","pages":"Pages 586-601"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057308","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}