TY - JOUR
T1 - An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction
AU - Xia, Hongjie
AU - Luo, Huanle
AU - Shan, Chao
AU - Muruato, Antonio E.
AU - Nunes, Bruno T.D.
AU - Medeiros, Daniele B.A.
AU - Zou, Jing
AU - Xie, Xuping
AU - Giraldo, Maria Isabel
AU - Vasconcelos, Pedro F.C.
AU - Weaver, Scott C.
AU - Wang, Tian
AU - Rajsbaum Gorodezky, Ricardo
AU - Shi, Pei Yong
N1 - Funding Information:
We thank Slobodan Paessler at University of Texas Medical Branch (UTMB) for providing Irf3−/− mice. We also thank other colleagues at UTMB for helpful discussions and support during the course of this study. P.-Y.S. lab was supported by University of Texas Medical Branch (UTMB) startup award, University of Texas STARs Award, CDC grant for the Western Gulf Center of Excellence for Vector-Borne Diseases, Pan American Health Organization grant SCON2016-01353, the Kleberg Foundation Award, UTMB CTSA UL1TR-001439, and NIH grant AI127744. This research was also partially supported by NIH grants AI120942 and AI099123 to S.C.W and T.W., respectively. R.R. lab is supported by NIH grants K12HD052023 from ORWH and NICHD, and NIH/NIAID R21 AI132479-01. P.F.C.V. was supported by projects of CAPES (Zika Fast-Track) and CNPq grants 440405/2016-5 and 303999/2016-0 from the Ministry of Science and Technology of Brazil and by the Ministry of Health.
Publisher Copyright:
© The Author(s) 2018.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Virus-host interactions determine an infection outcome. The Asian lineage of Zika virus (ZIKV), responsible for the recent epidemics, has fixed a mutation in the NS1 gene after 2012 that enhances mosquito infection. Here we report that the same mutation confers NS1 to inhibit interferon-β induction. This mutation enables NS1 binding to TBK1 and reduces TBK1 phosphorylation. Engineering the mutation into a pre-epidemic ZIKV strain debilitates the virus for interferon-β induction; reversing the mutation in an epidemic ZIKV strain invigorates the virus for interferon-β induction; these mutational effects are lost in IRF3-knockout cells. Additionally, ZIKV NS2A, NS2B, NS4A, NS4B, and NS5 can also suppress interferon-β production through targeting distinct components of the RIG-I pathway; however, for these proteins, no antagonistic difference is observed among various ZIKV strains. Our results support the mechanism that ZIKV has accumulated mutation(s) that increases the ability to evade immune response and potentiates infection and epidemics.
AB - Virus-host interactions determine an infection outcome. The Asian lineage of Zika virus (ZIKV), responsible for the recent epidemics, has fixed a mutation in the NS1 gene after 2012 that enhances mosquito infection. Here we report that the same mutation confers NS1 to inhibit interferon-β induction. This mutation enables NS1 binding to TBK1 and reduces TBK1 phosphorylation. Engineering the mutation into a pre-epidemic ZIKV strain debilitates the virus for interferon-β induction; reversing the mutation in an epidemic ZIKV strain invigorates the virus for interferon-β induction; these mutational effects are lost in IRF3-knockout cells. Additionally, ZIKV NS2A, NS2B, NS4A, NS4B, and NS5 can also suppress interferon-β production through targeting distinct components of the RIG-I pathway; however, for these proteins, no antagonistic difference is observed among various ZIKV strains. Our results support the mechanism that ZIKV has accumulated mutation(s) that increases the ability to evade immune response and potentiates infection and epidemics.
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U2 - 10.1038/s41467-017-02816-2
DO - 10.1038/s41467-017-02816-2
M3 - Article
C2 - 29379028
AN - SCOPUS:85041327442
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 414
ER -