Lineage-dependent differences and the role of IFITM3 in the type-I interferon-induced restriction of Zika virus

Type-I interferon (IFN-I) is an important aspect of host innate antiviral response. Recent studies have shown that IFN-I can inhibit Zika virus (ZIKV) replication and that this is mediated in part by Interferon-induced transmembrane protein 3 (IFITM3). ZIKV infections in South America have led to severe congenital syndrome in a subset of infected infants. ZIKV was first identified in Africa, where there is limited evidence for the pathogenic effects associated with the American outbreak, which is fueled by infection with Asian-lineage strains, raising the possibility that the African and Asian ZIKV lineages have distinct pathogenic properties. Given the observation that IFN-I can inhibit ZIKV replication in cell culture, we asked whether ZIKV strains differed in their susceptibility to IFN-I. There was a range of susceptibilities to IFN-I inhibition across virus strains. Virus production in A549 cells was reduced from 3-42-fold for IFNα and 63-807-fold for IFNβ across a panel of nine viruses, five from the African-lineage and four from the Asian-lineage. African-lineage ZIKV strains were more resistant to IFN-I than Asian-lineage strains, but this difference was only significant for IFNα-mediated restriction (p = 0.049). Notabl...Continue Reading