The zinc finger antiviral protein (ZAP) specifically inhibits the replication of Moloney murine leukemia virus (MLV) and Sindbis virus (SIN), but has very modest inhibitory effect on HIV. Previous studies suggest that ZAP directly binds to the viral RNA and recruit the RNA degradation machinery to degrade the target RNA. The HIV-1 Tat and Rev are regulatory proteins which bind to HIV RNA. Tat and Rev were fused with ZAP in various manners. Two fusion proteins, ZAP-Tat and ZAP-Rev were found to be able to inhibit the expression HIV-1 vector.