Endogenous ZAP is associated with altered global cellular gene expression during Zika virus infection

Abstract

The zinc finger antiviral protein 1 (ZAP) has broad antiviral activity. Previous RNA-seq analyses were conducted in uninfected wild-type and ZAP-KO cells; however, the impact of ZAP on global gene expression during virus infection remains unknown. Here, we characterized global cellular gene expression in uninfected and Zika virus-infected wild-type and ZAP knockout VERO cells. ZAP is an interferon (IFN)-stimulated gene, which itself may enhance type I IFN antiviral response. We found that ZAP was associated with the inhibition of Zika virus in the absence of a robust type I IFN system (VERO cells are deficient for IFN-alpha and -beta). Also, during Zika infection in VERO cells endogenous ZAP was associated with amplification of global transcriptional antiviral responses in the absence of a robust type I IFN system. Further studies are warranted to elucidate this type I IFN-independent antiviral activity directly or indirectly mediated by ZAP.