Virus-host interactions determine an
infection outcome. The
Asian lineage of
Zika vírus (
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-B 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-B induction; reversing the
mutation in an
epidemic ZIKV strain invigorates the
virus for
interferon-B induction; these mutational effects are lost in IRF3-knockout
cells. Additionally,
ZIKV NS2A, NS2B, NS4A, NS4B, and NS5 can also suppress
interferon-B
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.