Pub Date : 2025-06-01DOI: 10.1016/j.virs.2025.04.005
Yang Xu , Qiushi Zhang , Guoli Hou , Liang Hu , Tiaoyi Xiao , Xinyu Liang , Deliang Li , Junhua Li
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.
{"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":"<div><div>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.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 340-348"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","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}
Pub Date : 2025-06-01DOI: 10.1016/j.virs.2025.04.006
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
{"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":"40 3","pages":"Pages 495-498"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","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}
Pub Date : 2025-06-01DOI: 10.1016/j.virs.2025.05.004
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
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.
{"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":"<div><div>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.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 374-387"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","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}
Pub Date : 2025-06-01DOI: 10.1016/j.virs.2025.03.006
Yecheng Zhang , Xinlei Ji , Dan Huang , Gen Lu , Xinwen Chen
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of novel coronavirus disease 2019, can cause acute respiratory symptoms and even death globally. However, the immune escape mechanism and viral pathogenesis remain poorly understood. Here, we report that the SARS-CoV-2 3C-like (3CL) protease specifically cleaves gasdermin D (GSDMD) at Q29 and Q193, producing two N-terminal fragments, GSDMD1–29 and GSDMD1–193. We also found that SARS-CoV-2 infection induced the cleavage of GSDMD. Then, we demonstrated that the ability to cleave GSDMD was dependent on the protease activity of the 3CL protease. Interestingly, unlike the GSDMD1–275 fragment cleaved by caspase-1, GSDMD1–29 and GSDMD1–193 did not trigger pyroptosis or inhibit SARS-CoV-2 replication. Additionally, various RNA viral proteases display different preferences for cleaving GSDMD at Q29 and Q193. Our findings reveal a mechanism by which SARS-CoV-2 and other RNA viruses inhibit pyroptosis, highlighting the critical role of the 3CL protease in immune evasion and viral replication.
{"title":"The SARS-CoV-2 3CL protease inhibits pyroptosis through the cleavage of gasdermin D","authors":"Yecheng Zhang , Xinlei Ji , Dan Huang , Gen Lu , Xinwen Chen","doi":"10.1016/j.virs.2025.03.006","DOIUrl":"10.1016/j.virs.2025.03.006","url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of novel coronavirus disease 2019, can cause acute respiratory symptoms and even death globally. However, the immune escape mechanism and viral pathogenesis remain poorly understood. Here, we report that the SARS-CoV-2 3C-like (3CL) protease specifically cleaves gasdermin D (GSDMD) at Q29 and Q193, producing two N-terminal fragments, GSDMD<sub>1</sub><sub>–</sub><sub>29</sub> and GSDMD<sub>1</sub><sub>–</sub><sub>193</sub>. We also found that SARS-CoV-2 infection induced the cleavage of GSDMD. Then, we demonstrated that the ability to cleave GSDMD was dependent on the protease activity of the 3CL protease. Interestingly, unlike the GSDMD<sub>1–275</sub> fragment cleaved by caspase-1, GSDMD<sub>1</sub><sub>–</sub><sub>29</sub> and GSDMD<sub>1</sub><sub>–</sub><sub>193</sub> did not trigger pyroptosis or inhibit SARS-CoV-2 replication. Additionally, various RNA viral proteases display different preferences for cleaving GSDMD at Q29 and Q193. Our findings reveal a mechanism by which SARS-CoV-2 and other RNA viruses inhibit pyroptosis, highlighting the critical role of the 3CL protease in immune evasion and viral replication.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 324-332"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674581","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}
Pub Date : 2025-06-01DOI: 10.1016/j.virs.2025.04.004
Yan Ran , Zinuo Chen , Carolina Q. Sacramento , Lingyuan Fan , Qinghua Cui , Lijun Rong , Ruikun Du
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.
SARS-CoV-2变体和耐药突变体的出现强调了开发新型抗病毒药物的迫切需要。在本研究中，我们检测了中草药黄芩（Scutellaria barbata D. Don， SBD）在体外和体内对SARS-CoV-2感染的治疗作用。通过基于病毒复制子颗粒（VRP）的小鼠SARS-CoV-2感染模型，我们的研究发现，SBD提取物可以降低小鼠肺部病毒载量，减轻病毒诱导的肺炎。体外抗病毒实验进一步验证了SBD提取物对SARS-CoV-2复制的直接抗病毒作用。机制研究表明，SBD可以通过多种活性成分的组合，靶向3-凝乳胰蛋白酶样和木瓜蛋白酶样半胱氨酸蛋白酶，从而抑制SARS-CoV-2的复制。此外，SBD可以双向调节宿主的炎症反应，这也有助于减轻病毒诱导的急性肺损伤。总之，我们的研究提供了SBD作为对抗SARS-CoV-2感染的有希望的治疗剂，值得进一步开发。
{"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":"10.1016/j.virs.2025.04.004","url":null,"abstract":"<div><div>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, <em>Scutellaria barbata</em> D. Don (SBD), against SARS-CoV-2 infection both <em>in vitro</em> and <em>in vivo</em>. 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. <em>In vitro</em> 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.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 430-438"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","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}
Pub Date : 2025-06-01DOI: 10.1016/j.virs.2025.05.002
Jingyuan Zhang , Yaohui Fang , Chenhui Lin , Xiaoli Wu , Chaoxiong Yue , Fei Deng , Shu Shen
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.
{"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":"<div><div>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.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 361-373"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","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}
Pub Date : 2025-06-01DOI: 10.1016/j.virs.2025.05.010
Chong Wang , Muhan Huang , Bingyu Guo , Xi Zhou , Zongqiang Cui , Yi Xu , Yujie Ren
Enterovirus A71 (EV-A71) is the major causative pathogen for severe hand-foot-mouth disease (HFMD), a predominantly childhood-associated communicable disease. The mechanisms that children manifest severe disease progression while adults typically exhibit milder or asymptomatic infections remain incompletely characterized, which hinders the development of effective therapy against this disease. Herein, using the newborn mouse model of EV-A71 infection, we uncovered that the underdevelopment of T cells closely associated with the severity of EV-A71 infection, and EV-A71 infection dramatically impaired T-cell immune response. Moreover, the dysfunction of T-cell immunity contributes to the pathogenesis of EV-A71 infection, as the loss of T cells made neonatal mice highly vulnerable to EV-A71 infection. To further assess the relationship between T-cell immunity and HFMD, we enrolled a cohort of 145 pediatric patients with laboratory-confirmed EV-A71 infection and found that the compromised T-cell immune response is associated with the severity of EV-A71-caused HFMD in these children. Furthermore, we found that the treatment of newborn mice with Astragaloside A, a saponin from the medicinal herb Astragalus membranaceus, showed potent in vivo therapeutic efficacy against EV-A71 infection in a T-cell-dependent manner. In conclusion, these findings uncover the interaction between EV-A71 infection and T-cell immunity, provide novel insights onto the physiological impacts of T cells on the pathogenesis of EV-A71 infection and HFMD, and find a promising immunotherapeutic strategy to treat this viral disease.
{"title":"Severe enterovirus A71 infection is associated with dysfunction of T cell immune response and alleviated by Astragaloside A","authors":"Chong Wang , Muhan Huang , Bingyu Guo , Xi Zhou , Zongqiang Cui , Yi Xu , Yujie Ren","doi":"10.1016/j.virs.2025.05.010","DOIUrl":"10.1016/j.virs.2025.05.010","url":null,"abstract":"<div><div>Enterovirus A71 (EV-A71) is the major causative pathogen for severe hand-foot-mouth disease (HFMD), a predominantly childhood-associated communicable disease. The mechanisms that children manifest severe disease progression while adults typically exhibit milder or asymptomatic infections remain incompletely characterized, which hinders the development of effective therapy against this disease. Herein, using the newborn mouse model of EV-A71 infection, we uncovered that the underdevelopment of T cells closely associated with the severity of EV-A71 infection, and EV-A71 infection dramatically impaired T-cell immune response. Moreover, the dysfunction of T-cell immunity contributes to the pathogenesis of EV-A71 infection, as the loss of T cells made neonatal mice highly vulnerable to EV-A71 infection. To further assess the relationship between T-cell immunity and HFMD, we enrolled a cohort of 145 pediatric patients with laboratory-confirmed EV-A71 infection and found that the compromised T-cell immune response is associated with the severity of EV-A71-caused HFMD in these children. Furthermore, we found that the treatment of newborn mice with Astragaloside A, a saponin from the medicinal herb <em>Astragalus membranaceus</em>, showed potent <em>in vivo</em> therapeutic efficacy against EV-A71 infection in a T-cell-dependent manner. In conclusion, these findings uncover the interaction between EV-A71 infection and T-cell immunity, provide novel insights onto the physiological impacts of T cells on the pathogenesis of EV-A71 infection and HFMD, and find a promising immunotherapeutic strategy to treat this viral disease.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 451-461"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192265","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}
Pub Date : 2025-06-01DOI: 10.1016/j.virs.2025.03.008
Benli Huang , Sheng Chen , Zhanxin Wang , Keyu Feng , Yutao Teng , Ruoying Li , Guanming Shao , Jiaqian Rao , Xinheng Zhang , Qingmei Xie
Infectious bronchitis (IB), a highly contagious acute respiratory disease affecting avian species, poses significant challenges to poultry production. The causative agent, infectious bronchitis virus (IBV), exhibits a high mutation rate, leading to limited cross-protection by existing vaccines. This necessitates the development of novel vaccines. This study, based on preliminary investigations conducted by our research team, identified six potential strains (PYG QX1, ZQF QX2, FQH QX3, LYZ QX4, XXX QX5, and CSL strains) for vaccine development. Previous pathogenicity test and serum cross-neutralization experiments conducted in this study have demonstrated that the FQH QX3 strain exhibited the weakest pathogenicity and the broadest spectrum of serum neutralization, while the CSL strain showed the highest pathogenicity and was the most challenging to neutralize, posing the greatest difficulty in prevention and control. Subsequently, we constructed and rescued recombinant vaccine candidates, H120-FQH QX3, and H120-CSL, expressing the S1 and N proteins of the FQH QX3 and CSL strains, respectively. Immunization protection experiments indicated that the H120-CSL recombinant vaccine candidate exhibited the most effective immune protection, making it a promising candidate for further study and evaluation as a recombinant vaccine. The S1 and N genes of the CSL strain demonstrated strong immunogenicity, making them potential candidate antigen genes for future vaccine development.
{"title":"Development and immunoprotection assessment of novel vaccines for avian infectious bronchitis virus","authors":"Benli Huang , Sheng Chen , Zhanxin Wang , Keyu Feng , Yutao Teng , Ruoying Li , Guanming Shao , Jiaqian Rao , Xinheng Zhang , Qingmei Xie","doi":"10.1016/j.virs.2025.03.008","DOIUrl":"10.1016/j.virs.2025.03.008","url":null,"abstract":"<div><div>Infectious bronchitis (IB), a highly contagious acute respiratory disease affecting avian species, poses significant challenges to poultry production. The causative agent, infectious bronchitis virus (IBV), exhibits a high mutation rate, leading to limited cross-protection by existing vaccines. This necessitates the development of novel vaccines. This study, based on preliminary investigations conducted by our research team, identified six potential strains (PYG QX1, ZQF QX2, FQH QX3, LYZ QX4, XXX QX5, and CSL strains) for vaccine development. Previous pathogenicity test and serum cross-neutralization experiments conducted in this study have demonstrated that the FQH QX3 strain exhibited the weakest pathogenicity and the broadest spectrum of serum neutralization, while the CSL strain showed the highest pathogenicity and was the most challenging to neutralize, posing the greatest difficulty in prevention and control. Subsequently, we constructed and rescued recombinant vaccine candidates, H120-FQH QX3, and H120-CSL, expressing the S1 and N proteins of the FQH QX3 and CSL strains, respectively. Immunization protection experiments indicated that the H120-CSL recombinant vaccine candidate exhibited the most effective immune protection, making it a promising candidate for further study and evaluation as a recombinant vaccine. The <em>S1</em> and <em>N</em> genes of the CSL strain demonstrated strong immunogenicity, making them potential candidate antigen genes for future vaccine development.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 462-476"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732052","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}
Pub Date : 2025-06-01DOI: 10.1016/j.virs.2025.05.012
Shuting Zhou , Junrui Zhu , Houde Zhao , Zixin Huang , Kangqi Zheng , Fan Xia , Yufan Xu , Guocheng Zhao , Jijie Jiang , En Zhang , Haoyang Nian , Li Cui , Tao Sun , Xiangfeng Wang , Yanjun Zhou , Zhibiao Yang , Zhe Wang
Porcine epidemic diarrhea virus (PEDV) infection causes acute watery diarrhea in neonatal piglets, leading to substantial economic losses within the pig farming industry. This study demonstrates that clofazimine (CFZ) significantly inhibits PEDV replication in a dose-dependent manner in vitro, with negligible cytotoxicity. Findings from our time-of-addition assays indicate that CFZ effectively disrupts multiple stages of the viral infection cycle. Using a CoV-RdRp-Gluc reporter system, we evaluated the potency of CFZ against PEDV RNA-dependent RNA polymerase (RdRp), and determined a low IC50 value of 0.1364 μM. Molecular docking studies further confirmed that CFZ has high binding affinity at the active sites of the spike protein and RdRp protein in PEDV. Transcriptome analysis of Vero E6 cells, with and without CFZ treatment, revealed a significant change in transcriptional activity at 8 h post-infection (hpi). Moreover, the simultaneous application of CFZ and nucleoside analogs showed enhanced the anti-PEDV effect of CFZ in vitro. Our study underscores the potential of CFZ as a viable therapeutic agent against PEDV.
{"title":"Clofazimine targeting the spike protein and RdRp exhibits highly efficient antiviral activity against porcine epidemic diarrhea virus in vitro","authors":"Shuting Zhou , Junrui Zhu , Houde Zhao , Zixin Huang , Kangqi Zheng , Fan Xia , Yufan Xu , Guocheng Zhao , Jijie Jiang , En Zhang , Haoyang Nian , Li Cui , Tao Sun , Xiangfeng Wang , Yanjun Zhou , Zhibiao Yang , Zhe Wang","doi":"10.1016/j.virs.2025.05.012","DOIUrl":"10.1016/j.virs.2025.05.012","url":null,"abstract":"<div><div>Porcine epidemic diarrhea virus (PEDV) infection causes acute watery diarrhea in neonatal piglets, leading to substantial economic losses within the pig farming industry. This study demonstrates that clofazimine (CFZ) significantly inhibits PEDV replication in a dose-dependent manner <em>in vitro</em>, with negligible cytotoxicity. Findings from our time-of-addition assays indicate that CFZ effectively disrupts multiple stages of the viral infection cycle. Using a CoV-RdRp-Gluc reporter system, we evaluated the potency of CFZ against PEDV RNA-dependent RNA polymerase (RdRp), and determined a low IC<sub>50</sub> value of 0.1364 μM. Molecular docking studies further confirmed that CFZ has high binding affinity at the active sites of the spike protein and RdRp protein in PEDV. Transcriptome analysis of Vero E6 cells, with and without CFZ treatment, revealed a significant change in transcriptional activity at 8 h post-infection (hpi). Moreover, the simultaneous application of CFZ and nucleoside analogs showed enhanced the anti-PEDV effect of CFZ <em>in vitro</em>. Our study underscores the potential of CFZ as a viable therapeutic agent against PEDV.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 477-490"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217099","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号