Porcine reproductive and respiratory syndrome virus induces autophagy to promote virus replication

Abstract

An increasing number of studies demonstrate that autophagy, an intrinsic mechanism that can degrade cytoplasmic components, is involved in the infection processes of a variety of pathogens. It can be hijacked by various viruses to facilitate their replication. In this study, we found that PRRSV infection significantly increases the number of double- or single-membrane vesicles in the cytoplasm of host cells in ultrastructural analysis. Our results showed the LC3-I was converted into LC3-II after virus infection, suggesting the autophagy machinery was activated. We further used pharmacological agents and shRNAs to confirm that autophagy promoted the replication of PRRSV in host cells. Confocal microscopy analysis showed that PRRSV inhibited the fusion between autophagosomes and lysosomes, suggesting that PRRSV induced incomplete autophagy. This suppression caused the accumulation of autophagosomes which may serve as replication site to enhance PRRSV replication. It has been shown that NSP2 and NSP3 of arterivirus are two components of virus replication complex. We also found in our studies that NSP2 colocalized with LC3 in MARC-145 cells by performing confocal microscopy analysis and continuous density gradient centrifugation. Our studies presented here indicated that autophagy was activated during PRRSV infection and enhanced PRRSV replication in host cells by preventing autophagosome and lysosome fusion.

Autophagy Benefits the Replication of Newcastle Disease Virus in Chicken Cells and Tissues

“…The fact that UV-inactivated NDV could not trigger LC3 conversion suggests that viral replication is required to induce autophagy. Previous reports have indicated that some viruses, such as porcine reproductive and respiratory syndrome virus (PRRSV), HCV, and herpes simplex virus, induce an incomplete autophagic response by blocking autophagosome degradation (37)(38)(39). By several means of measuring autophagic flux, including monitoring p62 degradation, LC3-II turnover, and GFP-LC3 lysosomal delivery and proteolysis, we produced strong evidence that autophagic flux was enhanced upon NDV infection.…”

Hepatitis B virus promotes autophagic degradation but not replication in autophagosome

“…Thus, many pathogens, including viruses, have developed strategies for self-protection and further manipulate or utilize autophagy to their own advantages. For example, Epstein-Barr virus (EBV) and Kaposi's Sarcoma-Associated Herpes Virus (KSHV) negatively regulate autophagy during latency, whereas poliovirus (18,19), porcine reproductive and respiratory syndrome virus (PRRSV) (20), encephalomyocarditis virus (21), and picornavirus (22), utilize components of the autophagy pathway to promote viral replication. Some of the viruses use the autophagosome as a membrane structure to support its replication as well as to hijack it as a mechanism for releasing the packaged virions in a non-lytic manner.…”

“…This promotes the fusion of the autophagosome with the plasma membrane (12,19,21,23,24). While viruses promote autophagy induction, it has been shown that they have developed mechanisms to inhibit the maturation of autophagosomes by preventing the fusion between the autophagosome and the lysosome (19,20). However, recent findings also indicate that some RNA viruses benefit from autophagosome maturation.…”

Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro

“…Autophagy also contributes to innate and adaptive immunity against a wide variety of intracellular microbial pathogens, including bacteria, viruses and protozoa [14,15]. An increasing amount of evidences suggest that the autophagy processes are also exploited by many viruses for their replication, such as the measles virus (MeV) [16], PPRV [17], hepatitis C virus [18], classical swine fever virus (CSFV) [19], porcine reproductive and respiratory syndrome virus (PRRSV) [20], avian reovirus [21], and influenza A virus [22]. However, it has been demonstrated that autophagy is involved in the elimination of the herpes simplex virus [23], foot-and-mouth disease virus [24], human rotavirus [25] and cytomegalovirus [26].…”

“…Moreover, there are a variety of mechanisms by which the apoptotic and autophagic pathways are intertwined to affect cell fate [30]. It has been demonstrated that viruses can exploit autophagy and apoptosis for their replication [20,31,32]. A previous study suggested that autophagy can promote PRRSV replication by postponing apoptosis through the formation of a Bad-Beclin-1 complex [33].…”