Bovine viral diarrhea virus (BVDV) is classified into cytopathic (CP) and noncytopathic (NCP) types. Previous studies confirmed that NCP BVDV infection is the main cause of persistent infection and immune suppression in cattle, and its molecular mechanism of using host biological processes to evade immunity 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 Myeloid differentiation factor 88 (MyD88) were upregulated. Subsequently, we found that AV303 infection initiated autophagy but had degradation barriers, meanwhile the proliferation rate of MDBK cells increased. After knocking down MyD88, the cell proliferation rate was restored, and autophagy flow was activated utterly. Mechanistically, AV303 regulated cell proliferation by promoting ERK1/2 and Akt/mTOR, and both activities were inhibited after MyD88 is knocked down. The activity of MyD88 affected the degradation stage of autophagic flux. Treatment with autophagy agonists inhibits AV303 replication, whereas autophagy inhibitors enhance its replication. 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 identifies a novel mechanism in host-NCP BVDV interaction and highlights the potential of MyD88 as a target for anti-NCP BVDV drug development.

To Cite This Article: Wang K, Yang J, Y H, Xu J, Chen Y, Zhao Y, Umer S, Jiang K, Li X, 2025. MyD88 mediates noncytopathic bovine viral diarrhea virus replication by regulating cellular autophagy and proliferation. Pak Vet J, 45(1): 112-123. http://dx.doi.org/10.29261/pakvetj/2025.130