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Porcine reproductive and respiratory syndrome virus (PRRSV) is the leading virus known to cause massive economic loss in pig industry worldwide. In our previous study, transcriptional profiling of PRRSV-infected lung tissue of Tongcheng and Landrane pigs, which have highly pathogenic PRRSV (HP-PRRSV) susceptibility differences, showed differential expression of Rab11a. The small GTPase Rab11a regulates intracellular membrane trafficking events involved in autophagy. However, the involvement of the convergence of endosomal Rab11a and autophagy pathways during PRRSV infection is still unclear. In this study, we demonstrated that PRRSV infection induced complete autophagy and up-regulated the expression of Rab11a. Furthermore, interference of the expression of Rab11a resulted in the accumulation of endogenous LC3-II and p62, indicating that Rab11a played a vital role in autophagosome maturation. Silencing of Rab11a resulted in a compromise the expression of intracellular viral NSP2 and ORF7. Besides, confocal microscopy analysis showed that viral NSP2 was colocalized with Rab11a in Marc145 cells. Collectively, our findings revealed that Rab11a acted as a proviral host factor that benefited PRRSV replication in a manner that correlates with autophagy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Autophagy and apoptosis play significant roles in PRRSV infection and replication. However, the interaction between these 2 processes in PRRSV replication is still far from been completely understood. In our studies, the exposure of MARC-145 cells to PRRSV confirmed the activation of autophagy and subsequent induction of apoptosis. The inhibition of autophagy by 3-methyladenine (3-MA) caused a significant increase in PRRSV-induced apoptosis, showing a potential connection between both mechanisms. Moreover, we observed an increase in Bad expression (a pro-apoptotic protein) and Beclin1 (an autophagy regulator) in virus-infected cells up to 36h. Co-immunoprecipitation assays showed the formation of Bad and Beclin1 complex in PRRSV infected cells. Accordingly, Bad co-localized with Beclin1 in MARC-145 infected cells. Knockdown of Beclin1 significantly decreased PRRSV replication and PRRSV-induced autophagy, while Bad silencing resulted in increased autophagy and enhanced viral replication. Furthermore, PRRSV infection phosphorylated Bad (Ser112) to promote cellular survival. These results demonstrate that autophagy can favor PRRSV replication by postponing apoptosis through the formation of a Bad-Beclin1 complex.

Autophagy and apoptosis play essential roles 'in virus infection. Our study was performed to investigate the interplay between autophagy and apoptosis in PRRSV replication. In our present study, autophagy and apoptosis were induced by PRRSV infection. Viral replication was dampened/attenuated by autophagy deficient and potentiated by apoptosis inhibition. Furthermore, PRRSV replication was restored by apoptosis inhibition in autophagy deficient cells. Taken together, our findings unveil the functional relationship between autophagy and apoptosis during PRRSV replication. [ABSTRACT FROM AUTHOR]