Open AccessZika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro
Author(s) -
Yiming Wu,
Qingxiang Liu,
Jie Zhou,
Weidong Xie,
Cheng Chen,
Zefang Wang,
Haitao Yang,
Jun Cui
Publication year - 2017
Publication title -
cell discovery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.412
H-Index - 29
ISSN - 2056-5968
DOI - 10.1038/celldisc.2017.6
Subject(s) - zika virus , interferon , virology , ns3 , innate immune system , biology , virus , stat , autophagy , jak stat signaling pathway , in vitro , signal transduction , microbiology and biotechnology , apoptosis , immunology , immune system , hepatitis c virus , genetics , stat3 , tyrosine kinase
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.