The important role of TLR2/MyD88/JNK in regulating the pathogenesis and inflammation induced by pseudorabies virus in mice.

The host innate immune response plays a critical role in regulating and controlling viral infections by releasing inflammatory cytokines. Pseudorabies virus (PRV), a swine alphaherpesvirus, can cause severe encephalitis in piglets and various non-natural hosts. Previous studies demonstrated that PRV infection induced the significant elevation of pro-inflammatory cytokines levels and lethal inflammatory response in the mouse model. However, the underlying mechanisms responsible for activation and production of pro-inflammatory cytokines during PRV infection remain to be fully elucidated. In this study, we confirmed that PRV induced significant inflammatory response in C57BL/6 mice during its acute infection. Furthermore, TLR2/MyD88 axis was shown to be associated with the pathogenesis of PRV in mice. Specifically, TLR2/MyD88 axis was required for PRV-induced activation of NF-κB pathway and the subsequent pro-inflammatory cytokines expression. Meanwhile, MAPK/JNK and PI3K/Akt signaling pathways were also activated by TLR2/MyD88 axis and involved in regulating pro-inflammatory cytokines expression induced by PRV infection, respectively. Notably, administration of the JNK inhibitor (SP600125) could reduce clinical symptoms, alleviate pathological damage and prolong survival time of mice infected by PRV. Overall, this study strengthens our understanding upon the mechanism of host inflammatory response induced by PRV, and suggests that JNK signaling may act as a therapeutic target in controlling of PRV infection.