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 Isabel Giraldo, Pedro F.C. Vasconcelos, Scott C. Weaver, Tian Wang, Ricardo Rajsbaum, Pei Yong Shi

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


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
Issue number1
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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