Interferon-gamma-Directed Inhibition of a Novel High-Pathogenic Phlebovirus and Viral Antagonism of the Antiviral Signaling by Targeting STAT1
文献类型：期刊论文
| 作者 | Ning, Yun-Jia1; Mo, Qiong1,2; Feng, Kuan1,2; Min, Yuan-Qin1; Li, Mingyue3; Hou, Dianhai1; Peng, Cheng3; Zheng, Xin3; Deng, Fei1; Hu, Zhihong1 |
| 刊名 | FRONTIERS IN IMMUNOLOGY
 |
| 出版日期 | 2019-05-28 |
| 卷号 | 10页码:15 |
| 关键词 | IFN-gamma antiviral immunity STAT1 severe fever with thrombocytopenia syndrome virus (SFTSV) NSs inclusion body immune evasion virus-host interaction |
| ISSN号 | 1664-3224 |
| DOI | 10.3389/fimmu.2019.01182 |
| 英文摘要 | Severe fever with thrombocytopenia syndrome (SETS) is a life-threatening infectious disease caused by a novel phlebovirus, SETS virus (SFTSV). Currently, there is no vaccine or antiviral available and the viral pathogenesis remains largely unknown. In this study, we demonstrated that SFTSV infection results in substantial production of serum interferon-gamma (IFN-gamma) in patients and then that IFN-gamma in turn exhibits a robust anti-SFTSV activity in cultured cells, indicating the potential role of IFN-gamma in anti-SFTSV immune responses. However, the IFN-gamma anti-SFTSV efficacy was compromised once viral infection had been established. Consistently, we found that viral nonstructural protein (NSs) expression counteracts IFN-gamma signaling. By protein interaction analyses combined with mass spectrometry, we identified the transcription factor of IFN-gamma signaling pathway, STAT1, as the cellular target of SFTSV for IFN-gamma antagonism. Mechanistically, SFTSV blocks IFN-gamma-triggered STAT1 action through (1) NSs-STAT1 interaction-mediated sequestration of STAT1 into viral inclusion bodies and (2) viral infection-induced downregulation of STAT1 protein level. Finally, the efficacy of IFN-gamma as an anti-SFTSV drug in vivo was evaluated in a mouse infection model: IFN-gamma pretreatment but not posttreatment conferred significant protection to mice against lethal SFTSV infection, confirming IFN-gamma's anti-SFTSV effect and viral antagonism against IFN-gamma after the infection establishment. These findings present a picture of virus-host arm race and may promote not only the understanding of virus-host interactions and viral pathogenesis but also the development of antiviral therapeutics. |
| 资助项目 | National Natural Science Foundation of China[31600144] ; National Natural Science Foundation of China[31621061] ; Chinese Academy of Sciences[XDPB0301] ; National Key Research and Development Program of China[2018YFA0507202] ; National Key Research and Development Program of China[2016YFC1200400] ; National Key Research and Development Program of China[2016YFE0113500] ; European Union[653316] ; Wuhan Institute of Virology |
| WOS研究方向 | Immunology |
| 语种 | 英语 |
| WOS记录号 | WOS:000469269400001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/7385]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Wang, Hualin |
| 作者单位 | 1.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Hubei, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Huazhong Univ Sci & Technol, Tongji Med Coll, Inst Infect & Immunol, Dept Infect Dis,Union Hosp, Wuhan, Hubei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ning, Yun-Jia,Mo, Qiong,Feng, Kuan,et al. Interferon-gamma-Directed Inhibition of a Novel High-Pathogenic Phlebovirus and Viral Antagonism of the Antiviral Signaling by Targeting STAT1[J]. FRONTIERS IN IMMUNOLOGY,2019,10:15. |
| APA | Ning, Yun-Jia.,Mo, Qiong.,Feng, Kuan.,Min, Yuan-Qin.,Li, Mingyue.,...&Wang, Hualin.(2019).Interferon-gamma-Directed Inhibition of a Novel High-Pathogenic Phlebovirus and Viral Antagonism of the Antiviral Signaling by Targeting STAT1.FRONTIERS IN IMMUNOLOGY,10,15. |
| MLA | Ning, Yun-Jia,et al."Interferon-gamma-Directed Inhibition of a Novel High-Pathogenic Phlebovirus and Viral Antagonism of the Antiviral Signaling by Targeting STAT1".FRONTIERS IN IMMUNOLOGY 10(2019):15. |
入库方式： OAI收割
来源：武汉植物园
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