Host Zinc-finger CCHC-type containing protein 3 inhibits pseudorabies virus proliferation by regulating type I interferon signaling

Zinc finger CCHC-type containing protein 3 (ZCCHC3) acts as an antiviral factor that interacts with RIG-I and cGAS to modulate innate signaling against viral infections. Here, we investigated the role of porcine ZCCHC3 during pseudorabies virus (PRV) proliferation. We found that porcine ZCCHC3 plays an inhibitory role in the proliferation of PRV by regulating cellular innate immune responses. Further, overexpression of ZCCHC3 inhibited gB protein levels and viral titers, whereas knockdown of ZCCHC3 promoted viral growth. ZCCHC3 overexpression increased IFN-beta expression to upregulate downstream gene expression, thus leading to the suppression of viral replication. However, PRV infection reduced the endogenous expression of ZCCHC3 in permissive cells. Importantly, PRV-encoded UL13 and UL24 proteins were identified to inhibit the expression of ZCCHC3, thus antagonizing its antiviral effect. Collectively, our data underscore the important role of ZCCHC3 against PRV infection and promote understandings of viral proteins in PRV pathogenesis.

Automated summary

Porcine ZCCHC3 plays an inhibitory role in the proliferation of pseudorabies virus (PRV) by regulating cellular innate immune responses. Overexpression of ZCCHC3 inhibits viral titers and protein levels, while knockdown of ZCCHC3 promotes viral growth. ZCCHC3 overexpression upregulates IFN-beta expression to suppress viral replication. PRV infection reduces endogenous expression of ZCCHC3, and PRV-encoded UL13 and UL24 proteins inhibit ZCCHC3 expression, antagonizing its antiviral effect.