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Peste des petits ruminants virus (PPRV) is an important pathogen that seriously influences the productivity of small ruminants worldwide. We showed previously that PPRV induced sustained autophagy for their replication in host cells. Many studies have shown that exosomes released from virus-infected cells contain a variety of viral and host cellular factors that are able to modulate the recipient’s cellular response and result in productive infection of the recipient host. Here, we show that PPRV infection results in packaging of the viral genomic RNA and partial viral proteins into exosomes of Vero cells and upregulates exosome secretion. We provide evidence showing that the exosomal viral cargo can be transferred to and establish productive infection in a new target cell. Importantly, our study reveals that PPRV-induced autophagy enhances exosome secretion and exosome-mediated virus transmission. Additionally, our data show that TSG101 may be involved in the sorting of the infectious PPRV RNA into exosomes to facilitate the release of PPRV through the exosomal pathway. Taken together, our results suggest a novel mechanism involving autophagy and exosome-mediated PPRV intercellular transmission. IMPORTANCE Autophagy plays an important role in PPRV pathogenesis. The role of exosomes in viral infections is beginning to be appreciated. The present study examined the role of autophagy in secretion of infectious PPRV from Vero cells. Our data provided the first direct evidence that ATG7-mediated autophagy enhances exosome secretion and exosome-mediated PPRV transmission. TSG101 may be involved in the sorting of the infectious PPRV RNA genomes into exosomes to facilitate the release of PPRV through the exosomal pathway. Inhibition of PPRV-induced autophagy or TSG101 expression could be used as a strategy to block exosome-mediated virus transmission.

Peste des petits ruminants virus (PPRV) is an important pathogen that seriously influences the productivity of small ruminants worldwide. PPRV has evolved several mechanisms to evade IFN-I responses. We report that a novel microRNA in goat PBMCs, novel miR-3, was upregulated by PPRV to facilitate virus infection. Furthermore, PPRV V protein alone was sufficient to induce novel miR-3 expression, and NF-κB and p38 pathway may involved in the induction of novel miR-3 during PPRV infection. Importantly, we demonstrated that novel miR-3 was a potent negative regulator of IFN-α production by targeting IRAK1, which resulted in the enhancement of PPRV infection. In addition, we found that PPRV infection can activated ISGs through IFN independent and IRF3 dependent pathway. Moreover, our data revealed that novel miR-3 mediated regulation of IFN-α production may involve in the differential susceptibility between goat and sheep to PPRV. Taken together, our findings identified a new strategy taken by PPRV to escape IFN-I-mediated antiviral immune responses by engaging cellular microRNA and, thus, improve our understanding of its pathogenesis.IMPORTANCE: Peste des petits ruminants virus (PPRV) induce in the hosts a transient but severe immunosuppression, which threatens both small livestock and endangered susceptible wildlife populations in many countries. Despite extensive research has been explored, the mechanism underlying PPRV immune system evasion remains elusive. Our data provided the first direct evidence that novel microRNA-3 (novel miR-3) feedback inhibits type I IFN signaling when goat PBMCs are infected with PPRV vaccine strain N75/1, thus promoting the infection. In this study, the target of novel miR-3, IRAK1, which are important for PPRV-induced type I IFN production, have also been found. Moreover, we identified NF-κB and p38 pathways may involve in novel miR-3 induction in response to PPRV infection. Taken together, our research has provided new insight into understanding the effects of miRNA on host-virus interactions, and revealed a potential therapeutic target for antiviral intervention.

Peste des petits ruminants virus (PPRV) is an important pathogen that seriously influences the productivity of small ruminants worldwide. PPRV has evolved several mechanisms to evade type I interferon (IFN-I) responses. We report that a novel microRNA in goat peripheral blood mononuclear cells (PBMCs) called miR-3 is upregulated by PPRV to facilitate virus infection. Furthermore, PPRV V protein alone was sufficient to induce novel miR-3 expression, and NF-κB and p38 pathways may be involved in the induction of miR-3 during PPRV infection. Importantly, we demonstrated that miR-3 was a potent negative regulator of IFN-α production by targeting interleukin-1 receptor-associated kinase 1 (IRAK1), which resulted in the enhancement of PPRV infection. In addition, we found that PPRV infection can activate interferon-stimulated genes (ISGs) through IFN-independent and IRF3-dependent pathways. Moreover, our data revealed that miR-3-mediated regulation of IFN-α production may be involved in the differential susceptibility between goat and sheep to PPRV. Taken together, our findings identify a new strategy by PPRV to escape IFN-I-mediated antiviral immune responses by engaging cellular microRNA, and thus leads to improved understanding of PPRV pathogenesis. IMPORTANCE Peste des petits ruminants virus (PPRV) induces in the host a transient but severe immunosuppression, which threatens both small livestock and endangered susceptible wildlife populations in many countries. Despite extensive research, the mechanism underlying PPRV immune system evasion remains elusive. Our data provide the first direct evidence that a novel microRNA-3 (miR-3) feedback-inhibits type I IFN signaling when goat PBMCs are infected with PPRV vaccine strain N75/1, thus promoting the infection. In this study, the target of miR-3 was identified as IRAK1, which is important for type I IFN production. Moreover, we identified NF-κB and p38 pathways as possibly involved in miR-3 induction in response to PPRV infection. Taken together, our research has provided new insight into understanding the effects of miRNA on host-virus interactions, and revealed a potential therapeutic target for antiviral intervention.