Research Progress on the Roles and Mechanisms of Autophagy Involved in Porcine Reproductive and Respiratory Syndrome Virus Infection

Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped single-stranded positive sense RNA arterivirus. Infection by PRRSV results in porcine reproductive and respiratory syndrome (PRRS), characterized by abortions, stillbirths, weak-born piglets, and mummified fetuses in sows as well as respiratory diseases in pigs of all ages. PRRSV has caused tremendous economic losses to the global swine industry. Comprehensive investigation on PRRSV infection would be beneficial for the prevention and control of PRRS, and contribute to the high-quality development of the swine industry. Autophagy is a lysosome-dependent degradation and recycling process for abnormal proteins, damaged organelles, and invading pathogens. It comprises macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA), among which macroautophagy has been most extensively investigated so far, and is classified as non-selective autophagy and selective autophagy. Autophagy plays crucial roles in maintaining cellular homeostasis, controlling the quality of organelles, and transporting intracellular materials. Furthermore, autophagy is involved in diverse diseases, such as neurodegenerative diseases, autoimmune diseases, and cancers. Moreover, autophagy is a potent defense response to eliminate invading viruses, while viruses have evolved multiple strategies to subvert the autophagic degradation or even exploit autophagy for their own benefits. This review systematically scrutinized recent research progress on the roles and mechanisms of autophagy involved in PRRSV infection, and elaborated that autophagy played a dual role during PRRSV infection. On the one hand, PRRSV non-structural and structural proteins triggered macroautophagy (including reticulophagy, mitophagy, aggrephagy, and lipophagy) and CMA via a variety of mechanisms; in turn, macroautophagy and CMA facilitated PRRSV infection by participation in viral replication, antagonism of apoptosis, and inhibition of host immunity. On the other hand, selective autophagy (eg., reticulophagy) and CMA suppressed PRRSV infection by degradation of viral non-structural proteins and activation of antiviral immune responses. This review actually deepend the understanding of PRRSV infection from the autophagy perspective. In addition, this review summarized and raised certain controversial or unsolved issues, which provided clues for future studies on the roles and mechanisms of autophagy involved in PRRSV infection; in the meantime, this review illustrated and supported potential targets against autophagy for developing antiviral interventions to restrain PRRS epidemics.