Type I interferon (IFN) serves as the first line of defense against invading pathogens. Inhibition of IFN-triggered signaling cascade by Zika virus (ZIKV) plays a critical role for ZIKV to evade antiviral responses from host cells. Here we demonstrate that ZIKV nonstructural proteins NS1, NS4B and NS2B3 inhibit the induction of IFN and downstream IFN-stimulated genes through diverse strategies. NS1 and NS4B of ZIKV inhibit IFN beta signaling at TANK-binding kinase 1 level, whereas NS2B-NS3 of ZIKV impairs JAK-STAT signaling pathway by degrading Jak1 and reduces virus-induced apoptotic cell death. Furthermore, co-operation of NS1, NS4B and NS2B3 further enhances viral infection by blocking IFN-induced autophagic degradation of NS2B3. Hence, our study reveals a novel antagonistic system employing multiple ZIKV nonstructural proteins in restricting the innate antiviral responses.
基金：
National Key Basic Research Program of ChinaNational Basic Research Program of China [2015CB859800]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31522018, 31170832]; Guangdong Natural Science Funds for Distinguished Young Scholar [S2013050014772]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [15lgjc02]; Training Program for Outstanding Young Teachers in Higher Education institutions of Guangdong Province [YQ2015001]; Guangzhou Science and Technology Project [201605030012]; National Key Research Program of China [2016YFD0500300]
语种：
外文
被引次数：
WOS：
中科院(CAS)分区：
出版当年[2017]版：
无
最新[2023]版：
大类|1 区生物学
小类|2 区细胞生物学
第一作者：
第一作者机构：[1]Minist Educ, Sch Life Sci, State Key Lab Biocontrol, Key Lab Gene Engn, Guangzhou, Guangdong, Peoples R China;
通讯作者：
通讯机构：[1]Minist Educ, Sch Life Sci, State Key Lab Biocontrol, Key Lab Gene Engn, Guangzhou, Guangdong, Peoples R China;[2]Tianjin Univ, Sch Life Sci, Tianjin, Peoples R China;[3]Tianjin Int Joint Acad Biotechnol & Med, Tianjin, Peoples R China;[4]Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Guangzhou, Guangdong, Peoples R China
推荐引用方式(GB/T 7714)：
Wu Yaoxing,Liu Qingxiang,Zhou Jie,et al.Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro[J].CELL DISCOVERY.2017,3:-.doi:10.1038/celldisc.2017.6.
APA：
Wu, Yaoxing,Liu, Qingxiang,Zhou, Jie,Xie, Weihong,Chen, Cheng...&Cui, Jun.(2017).Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro.CELL DISCOVERY,3,
MLA：
Wu, Yaoxing,et al."Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro".CELL DISCOVERY 3.(2017):-
