Bovine herpesvirus-1 gE protein inhibits IFN- production to enhance replication by promoting MAVS ubiquitination and interfering with the interaction between IRF3 and CBP/p300

Bovine herpesvirus-1 (BoHV-1) can infect all breeds of cattle and cause respiratory and genital tract diseases. In the process of viral infection, viruses can use their own proteins to suppress the innate immunity of the host and promote its replication; however, the mechanism by which BoHV-1 evades the innate immune response is not fully understood. In this study, we found that rabbits inoculated with the live gene deletion vaccine BoHV-1-Delta gI/gE/TK generated higher interferon-beta (IFN-beta) production in the serum, liver, lung and kidney than rabbits inoculated with wt BoHV-1, which led to milder lesions in the lung and kidney. We performed gene deletion and ectopic expression experiments on viral proteins and found that gE was the major protein that inhibited IFN-beta expression. Further studies showed that MAVS and IRF3 were the targets of gE, and the specific mechanism was that gE inhibited IFN-beta production by promoting MAVS ubiquitination and interfering with the interaction between IRF3 and CBP/p300. These results suggest a new way of BoHV-1 inhibition of IFN-beta production to evade the host innate immunity.