ZCCHC3 inhibits PEDV proliferation by degrading nuclear coat proteins via the proteasome pathway.

Porcine epidemic diarrhea virus (PEDV) infection in pigs is characterized by vomiting, dehydration, and diarrhoea. The structural proteins of PEDV play crucial roles in viral entry, release, assembly, outgrowth, and host immune regulation. Similar to other viruses, PEDV primarily relies on host cellular mechanisms for productive infection. However, the host factors associated with PEDV infection remain undefined. Therefore, an in-depth understanding of the pathogenic mechanisms of PEDV is essential for comprehending this disease. Zinc-containing finger CCHC-type protein 3 (ZCCHC3) is an antiviral factor known to interact with RIG-I and cGAS, inhibiting the replication of pseudorabies virus (PRV). In this study, we investigated the role of porcine ZCCHC3 in PEDV proliferation. We first demonstrated that the expression of ZCCHC3 in LLC-PK1 cells is downregulated upon PEDV infection. Overexpression of ZCCHC3 inhibited PEDV replication, whereas knockdown of ZCCHC3 increased viral titer and N protein levels. Further studies revealed that ZCCHC3 interacts and co-localizes with N proteins, and that ZCCHC3-mediated antiviral effects depend on its zinc finger protease activity. Taken together, these findings provide valuable insights into the role of ZCCHC3 in PEDV proliferation and enhance our understanding of host-virus interactions.