LiCl inhibits PRRSV infection by enhancing Wnt/β-catenin pathway and suppressing inflammatory responses

Lithium chloride (LiCl) has been used as a mood stabilizer in the manic depressive disorders treatment. Recent studies show that LiCl is also a potent inhibitor for some DNA and RNA viruses. Porcine reproductive and respiratory syndrome virus (PRRSV) is an important viral pathogen in modern pig industry. In this study, we assessed the inhibitory effect of LiCl on PRRSV infection using plaque-formation assay, Q-PCR and Western blot analysis. Our results showed that LiCl could inhibit PRRSV infection in MARC-145 and PAM-CD163 cells. Previous reports have shown that LiCl could induce the Wnt pathway in the absence of Wnt ligands. In our studies, we demonstrated that LiCl activates the Wnt pathway in PRRSV infected cells. Additionally, the knockdown of β-catenin or the Wnt/β-catenin pathway inhibitor PNU74654 was able to reverse the antiviral effect of LiCl, which suggested that the inhibitory effect of LiCl against PRRSV replication might be associated with the activation of the Wnt/β-catenin pathway. We also found that lower viral replication after LiCl treatment was associated with the reduced mRNA levels of pro-inflammatory IL-8, IL-6, IL-1 β, tumor necrosis factor α and decreased NF-κB nuclear translocation. Collectively, our data demonstrated that LiCl inhibited PRRSV infection by enhancing Wnt/β-catenin pathway and suppressing pro-inflammatory responses.