Long noncoding RNA IRF1-AS is associated with peste des petits ruminants infection.

Peste des petits ruminants (PPR) is an acute and highly contagious disease and has long been a significant threat to small ruminant productivity worldwide. However, the molecular mechanism underlying host-PPRV interactions remains unclear and the long noncoding RNAs (lncRNAs) regulation of PPR virus (PPRV) infection has rarely been reported so far. Here, we first demonstrated that PPRV infection can induce an obvious innate immune response in caprine endometrial epithelial cells (EECs) at 48 h post-infection (hpi) with an MOI of 3. Subsequently, we determined that PPRV infection is associated with 191 significantly differentially expressed (SDE) lncRNAs, namely, 137 upregulated and 54 downregulated lncRNAs, in caprine EECs compared with mock control cells at 48 hpi by using deep sequencing technology. Importantly, bioinformatics preliminarily analyses revealed that these DE lncRNAs were closely related to the immune response. Furthermore, we identified a system of lncRNAs related to the immune response and focused on the role of lncRNA 10636385 (IRF1-AS) in regulating the innate immune response. Interestingly, we found that IRF1-AS was a potent positive regulator of IFN-ß and ISG production, which can significantly inhibit PPRV replication in host cells. In addition, our data revealed that IRF1-AS was positively correlated with its potential target gene, IRF1, which enhanced the activation of IRF3 and the expression of ISGs and interacted with IRF3. This study suggests that IRF1-AS could be a new host factor target for developing antiviral therapies against PPRV infection.

Peste des petits ruminants virus induces ERS-mediated autophagy to promote virus replication.

Peste des petits ruminants virus (PPRV) has long been a significant threat to small ruminant productivity worldwide. Virus infection-induced endoplasmic reticulum (ER) stress (ERS) and the subsequently activated unfolded protein response (UPR) play significant roles in viral replication and pathogenesis. However, the relationship between ERS and PPRV infection is unknown. In this study, we demonstrated that ERS was induced during PPRV infection in caprine endometrial epithelial cells (EECs). Importantly, we demonstrated that the induction of autophagy by PPRV was mediated by ERS. Furthermore, we found that the PERK/eIF2α pathway but not the ATF6 or IRE1 pathway was activated and that the activated PERK/eIF2α pathway participated in regulating ERS-mediated autophagy. Moreover, virus replication was required for PPRV infection-induced ERS-mediated autophagy and PERK pathway activation. Additionally, we revealed that either the viral nucleocapsid (N) or nonstructural protein C was sufficient to elicit ERS and activate the PERK/eIF2α pathway, which further increased autophagy. Taken together, these results suggest that PPRV N and C protein-induced autophagy enhances viral replication through the induction of ERS and that the PERK pathway may be involved in the activation of ERS-mediated autophagy during PPRV infection.