ZAP is a restriction factor for HCMV infection. (A) The expression of the ISG ZAP is induced at early stages during HCMV infection. The RNA-binding protein ZAP specifically binds to viral mRNAs transcribed from the HCMV UL4-UL6 genome locus (depicted in orange) and negatively affects their stability. In the presence of ZAP, expression of early and late HCMV genes and proteins, as well as genome replication, is delayed. (B) In the absence of ZAP, the stability of HCMV mRNAs transcribed from the UL4-UL6 locus is unaltered, and HCMV transcription, protein expression, and genome replication are enhanced compared to ZAP-expressing cells.