Virologica Sinica最新文献

{"title":"Eltrombopag, an FDA-approved drug, inhibits dengue virus type 2 by targeting NS2B-NS3 protease.","authors":"Xuerui Zhu, Xiao Gao, Yan Wu, Jia Lu, Xinlan Chen, Chenshu Zhao, Haoyu Li, Zhongfa Zhang, Shuwen Liu, Gengfu Xiao, Xiaoyan Pan","doi":"10.1016/j.virs.2025.05.009","DOIUrl":"10.1016/j.virs.2025.05.009","url":null,"abstract":"<p><p>Dengue viruses (DENV) have spread throughout the world and pose a huge threat to human life. The most widespread serotype is type 2 DENV (DENV 2), which has no specific treatment. NS2B-NS3 protease plays a pivotal role in DENV replication because of its function in cleavage of the viral polyprotein; thus, it is considered a promising target for antiviral discovery. In this study, we developed a high-throughput screening system based on the NS2B-NS3 protease to identify candidates from an FDA-approved drug library. Eltrombopag was screened out of 3273 drugs, and demonstrated inhibition on DENV 2 ​at the micromolar level in vitro, significantly reducing viral loads in the targeted organs of challenged mice following intraperitoneal injection. Further mechanistic analysis showed that eltrombopag allosterically binds to the DENV 2 NS2B-NS3 protease in a reversible, non-competitive manner, therefore inhibiting DENV 2 ​at the post-infection stage. In addition, eltrombopag inhibited the NS2B-NS3 proteases of DENV 4 and Zika virus, suggesting its potential as a broad-spectrum antiviral agent. This study repurposed eltrombopag as a promising antiviral agent against DENV, providing an alternative for antiviral development against flaviviruses.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188137","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":"Human endogenous retrovirus W family envelope protein (ERVWE1) regulates macroautophagy activation and micromitophagy inhibition via NOXA1 in schizophrenia.","authors":"Jiahang Zhang, Huiling Wang, Xing Xue, Xiulin Wu, Wenshi Li, Zhao Lv, Yaru Su, Mengqi Zhang, Kexin Zhao, Xu Zhang, Chen Jia, Fan Zhu","doi":"10.1016/j.virs.2025.05.007","DOIUrl":"10.1016/j.virs.2025.05.007","url":null,"abstract":"<p><p>The human endogenous retrovirus type W envelope glycoprotein (ERVWE1), located at chromosome 7q21-22, has been implicated in the pathophysiology of schizophrenia. Our previous studies have shown elevated ERVWE1 expression in schizophrenia patients. Growing evidence suggests that autophagy dysfunction contributes to schizophrenia, yet the relationship between ERVWE1 and autophagy remains unclear. In this study, bioinformatics analysis of the human prefrontal cortex RNA microarray dataset (GSE53987) revealed that differentially expressed genes were predominantly enriched in autophagy-related pathways. Clinical data further demonstrated that serum levels of microtubule-associated protein 1 light chain 3β (LC3B), a key marker of macroautophagy, were significantly elevated in schizophrenia patients compared to controls, and positively correlated with ERVWE1 expression. Cellular and molecular experiments suggested that ERVWE1 promoted macroautophagy by increasing the LC3B II/I ratio, enhancing autophagosome formation, and reducing sequestosome 1 (SQSTM1) expression via upregulation of NADPH oxidase activator 1 (NOXA1). Concurrently, NOXA1 downregulated the expression of key micromitophagy-related genes, including PTEN-induced kinase 1 (PINK1), Parkin RBR E3 ubiquitin-protein ligase (Parkin), and the pyruvate dehydrogenase E1 subunit α 1 (PDHA1). As a result, ERVWE1, via NOXA1, inhibited micromitophagy by suppressing the expression of PINK1, Parkin, and PDHA1, thereby leading to impaired production of mitochondrial-derived vesicles (MDVs). Mechanistically, ERVWE1 enhanced NOXA1 transcription by upregulating upstream transcription factor 2 (USF2). In conclusion, ERVWE1 promotes macroautophagy and inhibits micromitophagy through USF2-NOXA1 axis, providing novel mechanistic insight into the role autophagy dysregulation in schizophrenia. These findings suggest that targeting autophagy pathways may offer novel therapeutic strategies for schizophrenia treatment.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151995","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":"Compromised efferocytosis during aging is related to COVID-19 severity in mice.","authors":"Xianliang Ke, Xian Lin, Jin Wang, Minqi Chen, Xiaoqin Jian, Chang Ye, Quanjiao Chen","doi":"10.1016/j.virs.2025.05.008","DOIUrl":"10.1016/j.virs.2025.05.008","url":null,"abstract":"<p><p>Aging is one of the greatest risk factors for morbidity caused by the coronavirus disease 2019 (COVID-19). In older individuals, a dysregulated immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection contributes to disease severity; however, the underlying mechanism remains elusive. In this study, we established an aging mouse model of COVID-19, successfully replicating the development of a relatively severe disease in older adults. Further single-cell transcriptome analysis revealed a distinct immune cell landscape in the infected lungs, accompanied by an over-activated inflammatory response, especially in aging mice. Compared to young mice, aging mice showed extensive neutrophil activation, NETosis, and a dramatic decrease in the number of alveolar macrophages (AMs). Moreover, as important executors of efferocytosis, AMs exhibited a low efferocytotic gene signature and downregulation of multiple efferocytosis receptors in aged mice. Further analysis indicated that the efferocytosis of neutrophils, whether undergoing apoptosis or NETosis, was compromised after SARS-CoV-2 infection. Since efferocytosis is a key process in inflammatory resolution, impaired efferocytosis may contribute to hyperinflammation in aging lungs. Our study reveals the characteristics and role of efferocytosis in aging mice after SARS-CoV-2 infection and provides valuable insights for the potential treatment of COVID-19.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151992","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":"Host factor RBM25 promotes HBV replication through Yin Yang 1-mediated cccDNA transcription.","authors":"Yukun Li, Tianhao Mao, Liwei Zheng, Zhao Zhou, Qianqian Jiang, Xinyu Du, Ziyuan Ma, Xin Liu, Ting Zhang, Guochao Wei, Lin Wang, Yongzhen Liu, Xiaojing Zhang, Shourong Liu, Xiangmei Chen, Fengmin Lu","doi":"10.1016/j.virs.2025.05.004","DOIUrl":"10.1016/j.virs.2025.05.004","url":null,"abstract":"<p><p>The persistence of covalently closed circular DNA (cccDNA) in hepatitis B virus (HBV)-infected hepatocytes remains a major obstacle to effective antiviral treatment. Understanding the molecular mechanisms regulating HBV cccDNA transcription is essential for developing novel therapeutic strategies. In this study, we investigated the role of RNA binding motif protein 25 (RBM25) in HBV replication, focusing on its interaction with cccDNA and its regulation of host transcription factors. The results demonstrated that RBM25 knockdown markedly inhibited HBV replication, reducing levels of HBV DNA, hepatitis B e antigen (HBeAg), hepatitis B surface antigen (HBsAg), HBV RNA, and L-HBs in HBV-replicating and infected cell models. Consistent results were observed in a mouse model hydrodynamically injected with 1.2 ​× ​HBV plasmid. Conversely, RBM25 overexpression significantly enhanced HBV replication. Mechanistically, RBM25 promoted HBV promoter activities by binding to cccDNA through its RE/RD and PWI domains. This effect was mediated by increased Yin Yang 1 (YY1) expression, which enhanced acetylation of cccDNA-bound histones, promoting HBV transcription. Furthermore, RBM25 expression was upregulated and translocated to the nucleus following core protein expression and accumulation, while overexpression of RBM25 promoted core protein degradation. In conclusion, this study demonstrates that RBM25 is a novel host factor that enhances HBV replication by upregulating YY1-dependent transcriptional activation of cccDNA. It also reveales a reciprocal regulatory mechanism between the HBV core protein and RBM25, which helps sustain HBV replication.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143066","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":"Elevated interferon-induced transmembrane protein 3 in platelets and megakaryocytes suppresses Crimean-Congo hemorrhagic fever viral infection by interacting with glycoprotein Gc.","authors":"Jingyuan Zhang, Yaohui Fang, Chenhui Lin, Xiaoli Wu, Chaoxiong Yue, Fei Deng, Shu Shen","doi":"10.1016/j.virs.2025.05.002","DOIUrl":"10.1016/j.virs.2025.05.002","url":null,"abstract":"<p><p>Crimean-Congo hemorrhagic fever (CCHF) is a hemorrhagic fever caused by infection with the CCHF virus (CCHFV) and has a mortality rate of up to 30 ​%. Thrombocytopenia is a hallmark of CCHF; however, the mechanisms underlying this manifestation remain poorly understood. In addition to hemostasis, platelets play a crucial role in recognizing pathogens and mediating immune responses. We investigated the mechanisms underlying thrombocytopenia associated with CCHFV infection by analyzing the platelet transcriptome in mice. Interferon-induced transmembrane protein 3 (IFITM3), a known antiviral factor, was significantly upregulated. The role of IFITM3 in response to CCHFV infection was characterized using the human megakaryoblast cell line MEG-01, considered a parental cell line of platelets. Although the CCHFV infection rate was limited, MEG-01 ​cells maintained the infection and replication of CCHFV, leading to increased IFITM3 protein expression. We demonstrated that IFITM3 overexpression efficiently inhibited CCHFV infection, whereas IFITM3 knockout promoted viral infection. An interaction between IFITM3 and the CCHFV glycoprotein Gc was identified, which suppressed CCHFV entry into cells. The IFITM3 CIL-TMD domain is critical for this interaction. These results suggest that IFITM3 is a restriction factor and plays an antiviral role during CCHFV infection. Elevated expression of IFITM3 in platelets indicates that this could be a common mechanism by which platelets protect against viruses, including CCHFV, which may reduce platelet consumption and destruction caused by CCHFV infection. These findings provide valuable insights into the pathogenesis of CCHF-associated thrombocytopenia and offer foundational theoretical support for future therapeutic strategies.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132654","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":"Mutational landscapes of NITD008-resistant EV71 variants revealed through population sequencing.","authors":"Fang Yu, Qiu-Yan Zhang, Zhe-Rui Zhang, Cheng-Lin Deng, Bo Zhang","doi":"10.1016/j.virs.2025.05.003","DOIUrl":"10.1016/j.virs.2025.05.003","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132708","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":"Characterization of a SARS-CoV-2 infection model in golden hamsters with diabetes mellitus.","authors":"Hao-Feng Lin, Ren-Di Jiang, Rui-Xin Qin, Bing Yao, Wen-Tao Zeng, Yun Gao, Ai-Min Shi, Jian-Min Li, Mei-Qin Liu","doi":"10.1016/j.virs.2025.05.001","DOIUrl":"10.1016/j.virs.2025.05.001","url":null,"abstract":"<p><p>Being widespread across the globe, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and generating new variants and continuously poses threat to public health, especially to the population with chronic comorbidities. Diabetes mellitus is one of high-risk factors for severe outcome of coronavirus disease 2019 (COVID-19). Establishment of animal models that parallel the clinical and pathological features of COVID-19 complicated with diabetes is thus highly essential. Here, in this study, we constructed leptin receptor gene knockout hamsters with the phenotype of diabetes mellitus (db/db), and revealed that the diabetic hamsters were more susceptible to SARS-CoV-2 and its variants than wild-type hamsters. SARS-CoV-2 and its variants induced a stronger immune cytokine response in the lungs of diabetic hamsters than in wild-type hamsters. Comparative histopathology analyses also showed that infection of SARS-CoV-2 and the variants caused more severe lung tissue injury in diabetic hamsters, and may induce serious complications such as diabetic kidney disease and cardiac lesions. Our findings demonstrated that despite the decreased respiratory pathogenicity, the SARS-CoV-2 variants were still capable of impairing other organs such as kidney and heart in diabetic hamsters, suggesting that the risk of evolving SARS-CoV-2 variants to diabetic patients should never be neglected. This hamster model may help better understand the pathogenesis mechanism of severe COVID-19 in patients with diabetes. It will also aid in development and testing of effective therapeutics and prophylactic treatments against SARS-CoV-2 variants among these high-risk populations.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102769","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 mouse model of Crimean-Congo hemorrhagic fever virus-induced coagulopathy.","authors":"Hui Zhang, Ziyang Jiang, Haidang Liao, Jiang Li, Manli Wang, Yiwu Zhou, Zhihong Hu, Jia Liu","doi":"10.1016/j.virs.2025.04.008","DOIUrl":"10.1016/j.virs.2025.04.008","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044367","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 noninfectious pseudovirus system for an emerging orthoflavivirus.","authors":"Yanfan Shi, Yu He, Xiaoli Wang, Zhen Wu, Tao Wang, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Xinxin Zhao, Qiao Yang, Ying Wu, Shaqiu Zhang, Juan Huang, Xumin Ou, Di Sun, Anchun Cheng, Shun Chen","doi":"10.1016/j.virs.2025.04.006","DOIUrl":"10.1016/j.virs.2025.04.006","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029527","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":"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":"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 is exploited to facilitate KSHV lytic infection by inhibiting RTA deamidation. To be more specific, vGAT interacts with both RTA and cellular PFAS, and inhibits 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 appears to regulate the deamidation process of several viral ORFs of KSHV. Collectively, these findings unveil that a viral pseudo-enzyme is 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}