Bovine viral diarrhea virus suppresses type I IFN production by inducing MAVS degradation via autophagy mediated by the ROS-endoplasmic reticulum stress axis

Abstract

Bovine viral diarrhea virus (BVDV), the causative agent of bovine viral diarrhea-mucosal disease, is a major global threat to cattle health. BVDV employs sophisticated strategies to evade host defense and facilitate its replication. Understanding these mechanisms is crucial for developing effective vaccines and antiviral agents. Our study elucidates how cytopathic BVDV and non-cytopathic BVDV subvert the host’s antiviral innate immune response by exploiting autophagy to inhibit the RIG-I–MAVS pathway. A key finding is that BECN1-mediated autophagy directly targets MAVS protein for degradation via a specific BECN1 and MAVS interaction. Furthermore, we demonstrate that BVDV activates autophagy through ROS-ER stress axis to promote its replication. These insights reveal a novel immune evasion mechanism of BVDV and highlight the therapeutic potential of autophagy inhibition in treating BVDV-related diseases.