{"title":"Nucleophosmin 1 inhibits the replication of influenza A virus by competitively binding viral RNA with viral proteins.","authors":"Yingying Yu, Qian Wang, Yanli Wei, Junwen Liu, Guangwen Wang, Zhengxiang Wang, Wentao Shen, Lu Han, Chengjun Li, Cao-Qi Lei, Shuai Xu, Qiyun Zhu","doi":"10.1016/j.virs.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.virs.2025.04.007","url":null,"abstract":"<p><p>Influenza A viruses (IAVs) are single-stranded negative-sense RNA viruses that continually challenge animal and human health. In IAV-infected cells, host RNA-binding proteins play key roles in the life cycle of IAV by directly binding to viral RNA. Here, we examined the role of the host RNA-binding protein nucleophosmin-1 (NPM1) in IAV replication. We found that, as a nucleolar phosphoprotein, NPM1 directly binds to viral RNA (vRNA) and inhibits the replication of various subtypes of IAV. NPM1 binding to vRNA competitively reduces the assembly of the viral ribonucleoprotein complex and the viral polymerase activity, thereby reducing the generation of progeny viral RNA and virions. The RNA-binding activity of NPM1, with the key residues T199, T219, T234, and T237, is essential for its anti-influenza function. Taken together, our findings demonstrate that NPM1 acts as an RNA-binding protein and interacts with IAV vRNA to suppress viral replication.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016981","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 : 2025-04-12DOI: 10.1016/j.virs.2025.04.005
Yang Xu, Qiushi Zhang, Guoli Hou, Liang Hu, Tiaoyi Xiao, Xinyu Liang, Deliang Li, Junhua Li
{"title":"Viral pseudo-enzyme facilitates KSHV lytic replication via suppressing PFAS-mediated RTA deamidation.","authors":"Yang Xu, Qiushi Zhang, Guoli Hou, Liang Hu, Tiaoyi Xiao, Xinyu Liang, Deliang Li, Junhua Li","doi":"10.1016/j.virs.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.virs.2025.04.005","url":null,"abstract":"<p><p>Deamidation, a type of post-translational modification commonly considered a hallmark of protein \"aging\" and function decay, is increasingly recognized for its pivotal role in regulating biological processes and viral infection. Our previous study has demonstrated that the deamidation of replication and transcription activator (RTA), a master regulator of ubiquitous and oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV), mediated by phosphoribosylformylglycinamidine synthetase (PFAS), hinders its nuclear import and transcriptional activity. Here we report that the viral glutamine amidotransferase (vGAT) pseudo-enzyme was exploited to facilitate KSHV lytic infection by inhibiting RTA deamidation. To be more specific, vGAT interacted with both RTA and cellular PFAS, and inhibited PFAS-mediated RTA deamidation, thus facilitating RTA nuclear localization and suppressing nuclear factor-kappa B (NF-κB) signaling activation, as well as augmenting RTA-mediated transcriptional activation of viral open reading frames (ORFs). In addition, vGAT appeared to regulate the deamidation process of several viral ORFs of KSHV. Collectively, these findings unveil that a viral pseudo-enzyme was exploited to enhance viral infection via deamidation regulation.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987468","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 : 2025-04-12DOI: 10.1016/j.virs.2025.04.004
Yan Ran, Zinuo Chen, Carolina Q Sacramento, Lingyuan Fan, Qinghua Cui, Lijun Rong, Ruikun Du
{"title":"Scutellaria barbata D. Don extracts alleviate SARS-CoV-2 induced acute lung injury by inhibiting virus replication and bi-directional immune modulation.","authors":"Yan Ran, Zinuo Chen, Carolina Q Sacramento, Lingyuan Fan, Qinghua Cui, Lijun Rong, Ruikun Du","doi":"10.1016/j.virs.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.virs.2025.04.004","url":null,"abstract":"<p><p>The emergence of SARS-CoV-2 variants and drug-resistant mutants emphasizes the urgent need to develop novel antiviral agents. In the present study, we examined the therapeutic effect of the Chinese medicinal herb, Scutellaria barbata D. Don (SBD), against SARS-CoV-2 infection both in vitro and in vivo. Using a viral replicon particle (VRP)-based mouse model of SARS-CoV-2 infection, our study revealed that SBD extracts can reduce viral load in mouse lungs and alleviate the viral induced pneumonia. In vitro antiviral determination further validated the direct acting antiviral efficacy of SBD extracts against SARS-CoV-2 replication. Mechanistic studies demonstrated that SBD can act against SARS-CoV-2 replication by targeting both 3-chymotrypsin-like and papain-like cysteine proteases, via a combination of multiple active constituents. Moreover, SBD can modulate the host inflammation response in a bi-directional manner, which also contribute to the mitigation of viral induced acute lung injury. In summary, our study provides SBD as a promising therapeutic agent to combat SARS-CoV-2 infections that merit further development.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056142","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":"Differential susceptibility of immunodeficient mice to MPXV infection and the impact of various inoculation routes.","authors":"Xiaohan Wang, Shaowen Shi, Xiaoxuan Nie, Yongyang Sun, Jinglei Hu, Manlin He, Wenhao Ren, Yuxing Wang, Zhendong Guo, Gonghe Li, Changbo Ou, Xiao Li, Zongzheng Zhao","doi":"10.1016/j.virs.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.virs.2025.04.001","url":null,"abstract":"<p><p>Monkeypox virus (MPXV), a member of the Orthopoxvirus genus, caused a large-scale global outbreak in 2022. Developing mouse models for MPXV infection is crucial for advancing research on vaccines and therapeutic interventions. To address this, we conducted a comparative study on the susceptibility of six mouse strains-severe combined immune-deficiency (SCID), nude, genetically diabetic (db/db) and obese (ob/ob), C57BL/6J, and BALB/c-to MPXV infection. Mouse strains were infected with MPXV via intranasal inoculation, and body weight changes and mortality were monitored post-infection. Additionally, the tissue distribution of MPXV and the pathological changes in the lung tissues of the infected mice were evaluated. The results demonstrated that SCID and nude mice exhibited significant weight loss following MPXV infection, with 100 % mortality observed in SCID mice, while no mortality occurred in nude mice. In contrast, the other mouse strains showed no significant weight loss or mortality. Notably, the viral load in the lung tissues of SCID and nude mice was the highest among the tested strains. Furthermore, we investigated the impact of different inoculation routes-intranasal (I.N.), intraperitoneal (I.P.), and intravenous (I.V.)-on the pathogenicity of MPXV in mice. The results revealed that the intravenous route induced more pronounced pathogenic effects compared to the intranasal and intraperitoneal routes. In summary, this study provides valuable insights into the development of MPXV-infected mouse models, offering a foundation for further research on MPXV pathogenesis and therapeutic drug development.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050603","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 : 2025-04-07DOI: 10.1016/j.virs.2025.04.002
Qi Wang, Shi-Qiang Mei, Tian-Yi Dong, Jia Su, Yuan-Fei Pan, Yan Zhu, Ke Wu, Li-Biao Zhang, Mang Shi, Peng Zhou
{"title":"WITHDRAWN: Comparative metatranscriptome analysis in gut reveals insignificant host or microbiota changes in SARS-related coronavirus naturally infected bats.","authors":"Qi Wang, Shi-Qiang Mei, Tian-Yi Dong, Jia Su, Yuan-Fei Pan, Yan Zhu, Ke Wu, Li-Biao Zhang, Mang Shi, Peng Zhou","doi":"10.1016/j.virs.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.virs.2025.04.002","url":null,"abstract":"<p><p>The publisher regrets that this article has withdrawn.\u0000The full Elsevier Policy on Article Withdrawal can be found athttps://www.elsevier.com/about/policies-and-standards/article-withdrawal.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026119","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 : 2025-04-01DOI: 10.1016/j.virs.2025.03.010
Pei Wang , Buyun Tian , Ke Xiao , Wei Ji , Zonghong Li
{"title":"The SARS-CoV-2 NSP4 T492I mutation promotes double-membrane vesicle formation to facilitate transmission","authors":"Pei Wang , Buyun Tian , Ke Xiao , Wei Ji , Zonghong Li","doi":"10.1016/j.virs.2025.03.010","DOIUrl":"10.1016/j.virs.2025.03.010","url":null,"abstract":"<div><div>The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in mutations not only in the spike protein, aiding immune evasion, but also in the NSP3/4/6 proteins, crucial for regulating double-membrane vesicle (DMV) formation. However, the functional consequences of these NSP3/4/6 mutations remain poorly understood. In this study, a systematic analysis was conducted to investigate the evolutionary patterns of NSP3/4/6 mutations and their impact on DMV formation. The findings revealed that the NSP4 T492I mutation, a prevalent mutation found in all Delta and Omicron sub-lineages, notably enhances DMV formation. Mechanistically, the NSP4 T492I mutation enhances its homodimerization, leading to an increase in the size of puncta induced by NSP3/4, and also augments endoplasmic reticulum (ER) membrane curvature, resulting in a higher DMV density per fluorescent puncta. This study underscores the significance of the NSP4 T492I mutation in modulating DMV formation, with potential implications for the transmission dynamics of SARS-CoV-2. It contributes valuable insights into how these mutations impact viral replication and pathogenesis.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 2","pages":"Pages 225-235"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744063","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 : 2025-04-01DOI: 10.1016/j.virs.2025.03.013
Hai-Fan Zhao , Ying Wang , Xiao-Hong Liu , Xian-Hui Liu , Zhi Geng , Zeng-Qiang Gao , Li Huang , Chang-Jiang Weng , Yu-Hui Dong , Heng Zhang
{"title":"Structure-function insights into the dual role of African swine fever virus pB318L: A typical geranylgeranyl-diphosphate synthase and a nuclear import protein","authors":"Hai-Fan Zhao , Ying Wang , Xiao-Hong Liu , Xian-Hui Liu , Zhi Geng , Zeng-Qiang Gao , Li Huang , Chang-Jiang Weng , Yu-Hui Dong , Heng Zhang","doi":"10.1016/j.virs.2025.03.013","DOIUrl":"10.1016/j.virs.2025.03.013","url":null,"abstract":"<div><div>African swine fever virus (ASFV) pB318L is an important protein for viral replication that acts as a membrane-bound <em>trans</em>-geranylgeranyl-diphosphate synthase (GGPPS) catalyzing the condensation of isopentenyl diphosphate (IPP) with allylic diphosphates. Recently we solved the crystal structure pB318L lacking N-terminal transmembrane region and performed a preliminary structural analysis. In this study, structure-based mutagenesis study and geranylgeranyl pyrophosphate (GGPP) production assay further revealed the key residues for the GGPPS activity. Structural comparison showed pB318L displays a strong similarity to typical GGPPSs instead of protein prenyltransferases. The phylogenetic analysis indicated pB318L may share a common ancestor with the GGPPSs from <em>Brassicaceae</em> plants rather than from its natural host. The subcellular localization analysis showed pB318L is localized in both nucleus and cytoplasm (including the endoplasmic reticulum membrane and mitochondria outer membrane). A unique N-terminal nuclear localization signal (NLS) following the transmembrane region was discovered in pB318L and the NLS was confirmed to be required for the nuclear import. We further revealed the NLS plays an essential role in the interaction with nuclear transporter karyopherin subunit alpha 1 (KPNA1). Their interaction may suppress signal transducers and activators of transcription 1 (STAT1) translocation and subsequently competitively inhibit nuclear import of IFN-stimulated gene factor 3 (ISGF3) complex. Our biochemical, structural and cellular analyses provide novel insights to pB318L that acts as an essential GGPPS that promotes viral replication and as a nuclear import protein that may be involved in immune evasion of ASFV.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 2","pages":"Pages 236-246"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789053","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}