An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction

Hongjie Xia, Huanle Luo, Chao Shan, Antonio E. Muruato, Bruno T.D. Nunes, Daniele B.A. Medeiros, Jing Zou, Xuping Xie, Maria Giraldo Giraldo, Pedro F.C. Vasconcelos, Scott Weaver, Tian Wang, Ricardo Rajsbaum Gorodezky, Pei-Yong Shi

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number414
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

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interferon
viruses
mutations
Viruses
Interferons
induction
Mutation
Virus Activation
infectious diseases
Infection
Culicidae
Zika Virus
phosphorylation
Phosphorylation
reversing
genes
Genes
engineering
proteins

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction. / Xia, Hongjie; Luo, Huanle; Shan, Chao; Muruato, Antonio E.; Nunes, Bruno T.D.; Medeiros, Daniele B.A.; Zou, Jing; Xie, Xuping; Giraldo Giraldo, Maria; Vasconcelos, Pedro F.C.; Weaver, Scott; Wang, Tian; Rajsbaum Gorodezky, Ricardo; Shi, Pei-Yong.

In: Nature Communications, Vol. 9, No. 1, 414, 01.12.2018.

Research output: Contribution to journalArticle

Xia, Hongjie ; Luo, Huanle ; Shan, Chao ; Muruato, Antonio E. ; Nunes, Bruno T.D. ; Medeiros, Daniele B.A. ; Zou, Jing ; Xie, Xuping ; Giraldo Giraldo, Maria ; Vasconcelos, Pedro F.C. ; Weaver, Scott ; Wang, Tian ; Rajsbaum Gorodezky, Ricardo ; Shi, Pei-Yong. / An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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