Virologica Sinica最新文献_第6页

The SARS-CoV-2 3CL protease inhibits pyroptosis through the cleavage of gasdermin D sars - cov - 23cl蛋白酶通过裂解气皮蛋白D抑制焦亡。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.03.006

Yecheng Zhang , Xinlei Ji , Dan Huang , Gen Lu , Xinwen Chen

{"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}

引用次数: 0

Scutellaria barbata D. Don extracts alleviate SARS-CoV-2 induced acute lung injury by inhibiting virus replication and bi-directional immune modulation 黄芩提取物通过抑制病毒复制和双向免疫调节减轻SARS-CoV-2诱导的急性肺损伤。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2025-06-01 DOI: 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":"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}

引用次数: 0

Elevated interferon-induced transmembrane protein 3 in platelets and megakaryocytes suppresses Crimean-Congo hemorrhagic fever viral infection by interacting with glycoprotein Gc 血小板和巨核细胞中干扰素诱导的跨膜蛋白3升高通过与糖蛋白Gc相互作用抑制克里米亚-刚果出血热病毒感染。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.05.002

Jingyuan Zhang , Yaohui Fang , Chenhui Lin , Xiaoli Wu , Chaoxiong Yue , Fei Deng , Shu Shen

{"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}

引用次数: 0

Severe enterovirus A71 infection is associated with dysfunction of T cell immune response and alleviated by Astragaloside A 重度肠病毒A71感染与T细胞免疫应答功能障碍相关，黄芪甲苷A可减轻其免疫功能障碍。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.05.010

Chong Wang , Muhan Huang , Bingyu Guo , Xi Zhou , Zongqiang Cui , Yi Xu , Yujie Ren

{"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}

引用次数: 0

Mutational landscapes of NITD008-resistant EV71 variants revealed through population sequencing 通过群体测序揭示了nitd008抗性EV71变异的突变景观。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.05.003

Fang Yu , Qiu-Yan Zhang , Zhe-Rui Zhang , Cheng-Lin Deng , Bo Zhang

引用次数: 0

Development and immunoprotection assessment of novel vaccines for avian infectious bronchitis virus 禽传染性支气管炎病毒新型疫苗的研制及免疫保护效果评价。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2025-06-01 DOI: 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

{"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}

引用次数: 0

Clofazimine targeting the spike protein and RdRp exhibits highly efficient antiviral activity against porcine epidemic diarrhea virus in vitro 氯法齐明靶向刺突蛋白和RdRp对猪流行性腹泻病毒表现出高效的体外抗病毒活性。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2025-06-01 DOI: 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

{"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}

引用次数: 0

Coadministration of ribavirin and arenaviral entry inhibitor LHF-535 enhances antiviral benefit against authentic lassa virus 利巴韦林和沙粒病毒进入抑制剂LHF-535联合使用可增强对真正拉沙病毒的抗病毒作用。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.04.003

Cheng Peng , Jialing Hu , Yuan Bai , Wei Wu , Wenting Mao , Yang Liu , Yi Wan , Lei Zhang , Wei Li , Tingting Tian , Tiezhu Liu , Yanhai Wang , Mifang Liang , Jun Han , Zhiming Yuan , Jiandong Li , Chao Shan , Fei Deng , Wei Wang

引用次数: 0

Insights into cross-species infection: Porcine epidemic diarrhea virus infections in the rodent 冠状病毒跨物种感染的认识：猪流行性腹泻病毒在啮齿动物中的感染。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.03.012

Jianing Chen , Zemei Wang , Shengyu Lin , Mengling Gao , Yongheng Shao , Shuxian Li , Qingbo Chen , Yaru Cui , Yonghao Hu , Guangliang Liu

{"title":"Insights into cross-species infection: Porcine epidemic diarrhea virus infections in the rodent","authors":"Jianing Chen , Zemei Wang , Shengyu Lin , Mengling Gao , Yongheng Shao , Shuxian Li , Qingbo Chen , Yaru Cui , Yonghao Hu , Guangliang Liu","doi":"10.1016/j.virs.2025.03.012","DOIUrl":"10.1016/j.virs.2025.03.012","url":null,"abstract":"<div><div>The cross-species infection of coronaviruses has resulted in several major epidemics since 2003. Porcine epidemic diarrhea virus (PEDV) is a devastating swine enteric coronavirus, which targets pigs as the only natural reservoir. In this study, the nucleic acid of PEDV was detected in rat fecal samples collected from pig farms. Further animal tests showed that PEDV can cause systemic infections in neonatal mice and rats via intracranial inoculation. The brain, lung, intestine and spleen were all targets for PEDV in rodents in contrast to the intestine being targeted in pigs. Morbidity and mortality vary via different infection routes. PEDV was also detectable in feces after infection, suggesting that the infected rodents were potential infectious sources. Moreover, the cerebral tropism of PEDV was verified in piglets via orally inoculation, which had not been identified before. In conclusion, our findings demonstrate that PEDV could cross the species barrier to infect mice and rats through different routes in experimental settings. Although it is highly devastating to piglets, PEDV changes the target organs and turns to be milder when meeting with new hosts. Based on these findings, more attention should be paid to the potential cross-species infection of PEDV.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 301-313"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744051","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}

引用次数: 0

A mouse model of Crimean-Congo hemorrhagic fever virus-induced coagulopathy 克里米亚-刚果出血热病毒致凝血病小鼠模型。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.04.008

Hui Zhang , Ziyang Jiang , Haidang Liao , Jiang Li , Manli Wang , Yiwu Zhou , Zhihong Hu , Jia Liu

引用次数: 0