ZAP modulates global cellular gene expression under steady-state condition and during Zika virus infection

The zinc finger CCCH-type antiviral protein 1 (ZAP) exhibits broad antiviral activity. Previous global gene expression analyses were conducted in uninfected wild-type and ZAP-KO HeLa cells; however, the impact of ZAP on gene expression during virus infection remains unknown. Here, we characterized global cellular gene expression under steady-state condition and during Zika virus infection in wild-type and ZAP knockout VERO cells. Additionally, we compared Zika virus RNA loads in wild-type and ZAP knockout VERO cells. Our findings indicate that endogenous ZAP is associated with the inhibition of intracellular Zika virus RNA loads. In addition to its direct interaction with viral RNA, ZAP enhances type I interferon (IFN) antiviral responses. Interestingly, during Zika infection, endogenous ZAP amplified antiviral responses at the gene expression level, in the absence of a robust type I IFN system (VERO cells are deficient for IFNs alpha and beta). Our study highlights the role of ZAP in enhancing cellular responses against Zika virus, even in the absence of a robust type I IFN system. Further studies are warranted to elucidate this ZAP-mediated type I IFN-independent antiviral activity.