Glycogen synthase kinase 3ß (GSK3ß) modulates antiviral activity of zinc-finger antiviral protein (ZAP).

Zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses, including HIV-1, Ebola virus, and Sindbis virus. ZAP binds directly to specific viral mRNAs and recruits cellular mRNA degradation machinery to degrade the target RNA. ZAP has also been suggested to repress translation of the target mRNA. In this study, we report that ZAP is phosphorylated by glycogen synthase kinase 3ß (GSK3ß). GSK3ß sequentially phosphorylated Ser-270, Ser-266, Ser-262, and Ser-257 of rat ZAP. Inhibition of GSK3ß by inhibitor SB216763 or down-regulation of GSK3ß by RNAi reduced the antiviral activity of ZAP. These results indicate that phosphorylation of ZAP by GSK3ß modulates ZAP activity.