title: Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteinsin vitro.
abstract: 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 IFNβ 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.
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences , Guangzhou, China.
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences , Guangzhou, China.
authors.forename: Qingxiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences , Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences , Guangzhou, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Xie
authors.affiliation: School of Life Sciences, Tianjin University , Tianjin, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Tianjin University , Tianjin, China.
authors.forename: Zefang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin, China; Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Guangzhou, China; Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cui
keywords: Zika virus; antiviral immunity; nonstructural proteins; type I interferon signaling