Zinc finger antiviral protein (ZAP) inhibits PCV2 replication by targeting ORF1, ORF2 and ORF3 mRNA.

Porcine circovirus type 2 (PCV2) is the primary cause of post-weaning multisystemic wasting syndrome (PMWS) and other PCV-associated diseases (PCVAD). Here we report the antiviral properties of porcine ZAP long isoform (pZAPL), encoded by ZC3HAV1 gene, against PCV2, a single-stranded circular DNA virus. The expression of porcine ZAP responds to PCV2 infection in vivo and in vitro. Notably, the antiviral activity of pZAPL appears to be stronger than short isoform of pZAP (pZAPS). Further dual luciferase and RNA immunoprecipitation analyses showed that pZAPL targeted the ORF1, ORF2 and ORF3 mRNAs of PCV2. Overexpression of pZAPL could impact the mRNA stability of ORF1, ORF2, and ORF3. In summary, porcine ZAPL inhibits the replication of PCV2 by targeting the mRNA of ORF1, ORF2 and ORF3. The findings from this study further extend the understanding of the role of pZAP in porcine antiviral innate immunity.