Virologica SinicaPub Date : 2026-09-19DOI: 10.1016/j.virs.2026.04.009
Yue Zhang, Xiu-Li Yan, Kao Deng, Meng-Jiao He, Hui Wang, Zi-Jin Cui, Yu-Yan Li, Lei Cao, Wenlong Ma, Byung-Ho Kang, Hoi Ki Leung, Peter Pak-Hang Cheung, Cheng-Feng Qin, Ming-Yuan Li, Xiao-Feng Li
{"title":"EHD4 facilitates Zika virus infection by regulating extracellular vesicle-associated viral release and cell attachment.","authors":"Yue Zhang, Xiu-Li Yan, Kao Deng, Meng-Jiao He, Hui Wang, Zi-Jin Cui, Yu-Yan Li, Lei Cao, Wenlong Ma, Byung-Ho Kang, Hoi Ki Leung, Peter Pak-Hang Cheung, Cheng-Feng Qin, Ming-Yuan Li, Xiao-Feng Li","doi":"10.1016/j.virs.2026.04.009","DOIUrl":"10.1016/j.virs.2026.04.009","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) and other extracellular membrane-associated particles can contribute to viral dissemination; however, the host factors that regulate the composition and infectivity of EV-associated viral material remain incompletely understood. Here, comparative proteomic profiling identified Eps15 homology domain-containing protein 4 (EHD4) as a candidate host factor enriched in EV/virion-containing preparations from Zika virus (ZIKV)-infected Vero cells. Genetic ablation of EHD4 in HeLa cells impaired the propagation of ZIKV, Japanese encephalitis virus, and dengue virus serotype 2, whereas EHD4 re-expression restored viral propagation. In ZIKV-infected EHD4-knockout (KO) cells, a greater proportion of extracellular viral RNA was recovered in EV-enriched fractions than in wild-type (WT) cells. However, viral material recovered from KO-derived EV-enriched fractions exhibited reduced cell-binding activity and lower infectivity. Partial disruption of membrane integrity attenuated the difference in infectivity between WT- and KO-derived preparations, suggesting that membrane-associated components contribute to the functional properties of the associated viral material. ZIKV replicon assays showed no major effect of EHD4 on viral RNA replication. Immunofluorescence showed partial colocalization of EHD4 with CD63-positive compartments and ZIKV envelope protein. Transmission electron microscopy revealed that EHD4 loss did not affect multivesicular body (MVB) formation, but virus-like particles were readily observed in MVB lumens of WT cells and rarely in KO cells, suggesting that EHD4 promotes viral sorting into MVB luminal vesicles. Quantitative proteomic analysis further identified reduced abundance of a subset of membrane-associated proteins in KO-derived EV-enriched fractions. Collectively, these findings identify EHD4 as a host factor that influences the extracellular partitioning, composition, and infectivity of flaviviral material recovered in EV-enriched fractions. The molecular mechanisms underlying these effects remain to be defined.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002621","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 : 2026-09-17DOI: 10.1016/j.virs.2026.09.007
Ting Shu, Mengyu Hu, Yiyang Li, Mengge Han, Xingyue Wang, Qi Cheng, Xiqiu Xu, Yang Qiu, Xi Zhou
{"title":"Flavivirus NS1 possesses NTPase and RNA helix unwinding activities.","authors":"Ting Shu, Mengyu Hu, Yiyang Li, Mengge Han, Xingyue Wang, Qi Cheng, Xiqiu Xu, Yang Qiu, Xi Zhou","doi":"10.1016/j.virs.2026.09.007","DOIUrl":"10.1016/j.virs.2026.09.007","url":null,"abstract":"<p><p>Flaviviruses are a group of arthropod-borne positive-sense RNA viruses, including Zika virus (ZIKV), dengue virus 2 (DENV2) and Japanese encephalitis virus (JEV). For RNA viruses, RNA helicases play critical roles in viral replication by unwinding double-stranded RNA intermediates generated in viral life cycles by remodeling viral RNA structures. Here, we report that NS1 proteins from ZIKV, DENV2 and JEV, possesse NTPase and RNA helix unwinding activities. ZIKV NS1 unwinds dsRNA in an NTP-dependent manner with 5' → 3' directionality, and its unwinding activity is broad-spectrum, targeting dsRNA, dsDNA and RNA/DNA hybrids. Moreover, both DENV2 and JEV NS1 also display NTPase and helicase activities, but they differ in substrate preference and directionality: JEV NS1 unwinds in the 5' → 3' direction like ZIKV NS1, whereas DENV2 NS1 unwinds only shorter duplexes and shows 3' → 5' directionality. Mutagenesis identified the basic residue at position 211 (arginine in ZIKV, lysine in DENV2/JEV) as critical for the unwinding activity of ZIKV and JEV NS1, but dispensable for DENV2 NS1. These findings indicate that flavivirus NS1 represents a previously unrecognized non-canonical RNA helicase, suggesting that NS1 may have the capacity to participate in RNA remodeling processes.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991489","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 : 2026-09-11DOI: 10.1016/j.virs.2026.09.005
Lu Zhang, Ryan Hisner, Markus Hoffmann, Stefan Pöhlmann
{"title":"Update on BA.3.2 epidemiology: Evidence for co-circulation and preferential infection of children.","authors":"Lu Zhang, Ryan Hisner, Markus Hoffmann, Stefan Pöhlmann","doi":"10.1016/j.virs.2026.09.005","DOIUrl":"10.1016/j.virs.2026.09.005","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945803","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 : 2026-09-10DOI: 10.1016/j.virs.2026.09.004
Yuxin Shao, Xinyu Wang, Ziyi Su, Yueping Zeng, Guoshuang Feng, Zhengde Xie, Ran Wang
{"title":"Epidemiological characteristics and in-hospital burden of infectious mononucleosis among hospitalized children in China, 2021-2023.","authors":"Yuxin Shao, Xinyu Wang, Ziyi Su, Yueping Zeng, Guoshuang Feng, Zhengde Xie, Ran Wang","doi":"10.1016/j.virs.2026.09.004","DOIUrl":"10.1016/j.virs.2026.09.004","url":null,"abstract":"<p><p>This multicenter study described the epidemiological characteristics, recorded first-ranked secondary diagnoses, and in-hospital burden of pediatric infectious mononucleosis (IM) hospitalizations in China during 2021-2023. Data were obtained from the FUTURE database. We identified hospitalizations with IM as the principal discharge diagnosis from discharge-record front pages at 31 tertiary children's hospitals between January 1, 2021, and December 31, 2023, and analyzed demographic, geographic, temporal, diagnostic, length-of-stay (LOS), and expense data using descriptive statistics and multivariable regression. Among 15,239 IM hospitalizations, representing 0.42% of all hospitalizations, the male-to-female ratio was 1.34. Children aged 4-6 years comprised the largest group, followed by those aged 1-3 and 7-12 years; 70.32% were urban residents, and admissions peaked in August and September. After adjustment for age, sex, seven-category geographic area, and month, the proportion of IM hospitalizations among all hospitalizations was lower in 2023 than in 2021-2022 (adjusted rate ratio, 0.822; 95% CI, 0.784-0.861; P < 0.001). A first-ranked secondary diagnosis was recorded in 68.29% of cases; bronchitis/pneumonia was the most common category, followed by hepatic dysfunction. Median LOS was 7 days, and median hospitalization expense was CNY 5563.07. Encephalitis was recorded in only 15 cases, which had the highest observed median LOS and hospitalization expenses. These findings provide a large multicenter baseline for the epidemiological patterns and in-hospital burden of pediatric IM hospitalizations across participating tertiary children's hospitals in China and may inform future surveillance and resource planning.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930748","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 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":"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":"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":"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":"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":"2026-08-28","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}