MyD88 mediates noncytopathic bovine viral diarrhea virus replication by regulating cellular autophagy and proliferation

Bovine viral diarrhea virus(BVDV) is classified into cytopathic (CP) and noncytopathic (NCP) types. Previous studies have confirmed that NCP BVDV infection is the main cause of persistent infection and immune suppression in cattle, and the molecular mechanism of its immune evasion remains unclear. We initially examined the replication of the AV303 strain (NCP BVDV) in MDBK cells at different time points. Proteomic analysis at the peak replication time point revealed that the TLR signaling pathway and the adaptor protein MyD88 were upregulated. We subsequently confirmed that AV303 induced autophagy and proliferation in cells, as indicated by increased autophagic activity and cell proliferation rates following viral infection. Knocking down MyD88 downregulated the virus-induced activation of autophagy and proliferation. Mechanistically, AV303 regulates cell proliferation by promoting ERK1/2 and mTOR, and ERK1/2 activity is inhibited after MyD88 is knocked down. AV303 replication levels increased with autophagy activation and decreased with autophagy inhibition. This study demonstrates that the activity of MyD88 mediated by the AV303 strain can regulate host cell autophagy and proliferation, creating advantageous conditions for its replication. This study demonstrates a new mechanism host-NCP BVDV interaction and the potential of MyD88 as a novel anti-NCP BVDV drug.