Cytoplasmic translocation of tripartite motif-containing 28 is critical for PRRSV-induced autophagy through promoting Vps34-Beclin1 complex formation.

Autophagy, as a highly conserved cellular metabolic regulation mechanism, is a double-edged sword and plays multiple roles in viral infections processes. As a member of the Arteriviridae family within the order Nidovirales, the porcine reproductive and respiratory syndrome virus (PRRSV) induces cell autophagy both IMPORTANCE: PRRS is one of the major diseases affecting the global swine industry. Infection with PRRSV can cause respiratory disease in pigs of all ages and reproductive disorders in sows. Therefore, understanding the interaction between PRRSV and host factors may help to develop new antiviral strategies against PRRSV. We found that PRRSV Nsp4 was important for nuclear export of TRIM28 in a CRM1-dependent manner during PRRSV infection. TRIM28 in the cytoplasm increases the formation of VPS34-Beclin1 complex by interacting with Vps34, further initiating autophagy. Hence, our study reveals a novel mechanism of PRRSV-mediated autophagy and provides valuable information for further understanding the pathogenesis of PRRS, which might contribute to the development of novel antiviral drugs.