The canonical Wnt/?-catenin signaling pathway facilitates pseudorabies virus proliferation and enhances virus-induced autophagy

Pseudorabies virus (PRV) is a swine herpesvirus with a broad host range that causes significant economic losses worldwide. The Wnt/beta-catenin signaling pathway is reportedly involved in multiple viruses' proliferation. In this study, we demonstrated that PRV infection significantly activated the Wnt/beta-catenin signaling and promoted the nuclear translocation of beta-catenin. Applying specific chemical inhibitors (FH535 and iCRT14) caused a remarkable decrease in PRV titers in various cell lines. Knockdown of beta-catenin by siRNA also reduced the proliferation of PRV. On the contrary, treatment with lithium chloride (LiCl), an inhibitor of GSK3 beta, stimulated the Wnt/beta-catenin signaling pathway and enhanced the PRV proliferation. Similarly, overexpression of beta-catenin promoted PRV proliferation and reversed the antiviral effect of FH535. Moreover, LiCl promoted PRV-induced autophagy, whereas FH535 and iCRT14 showed converse effects. These findings suggest that PRV infection stimulates the canonical Wnt/beta-catenin signaling pathway, facilitating PRV proliferation and regulating virusinduced autophagy. These data also provide potential targets for developing antiviral agents against PRV.