Porcine ISG15 modulates the antiviral response during pseudorabies virus replication

Pseudorabies virus (PRV) is one of the most vital pathogens of swine, leading to huge economic losses to the pig industry. Functioning in innate immunity, type-I interferon (IFN) plays a vital role in initial stage of viral infection. ISG15, an IFN-stimulated ubiquitin-like protein, is highly increased during virus infection and participates in the IFN-mediated antiviral immune response. However, limited attention has been paid to the functional role of porcine ISG15 (pISG15) in PRV infection. In this study, we generated a PK15 inducible cell line stably expressing the pISG15 gene and investigated the potential anti-PRV response of pISG15. We demonstrated that pISG15 was upregulated in an early stage of PRV infection, and pISG15 overexpression efficiently inhibited PRV replication by reducing the viral titers and mRNA levels of PRV, and also increased expression of IFN-β and activation of the ISRE promoter. However, knockdown of pISG15 by siRNA did not affect PRV replication, and potentiated IFN-I-mediated signaling, resulting in an increase in antiviral response in the process of PRV infection. The results showed that pISG15 has a potential immunodulatory role in cellular antiviral response against PRV.