Project description:We report the application of MeRIP-seq (m6A-specific methylated RNA immunoprecipitation) for m6A site profiling of lung tissue under Peste des petits ruminants virus (PPRV) infection.
Project description:Peste des petits ruminants virus (PPRV) belongs to the genus Morbillivirus that causes an acute and highly contagious disease in goats and sheep. Virus infection can trigger the change in the cellular microRNA (miRNA) expression profile, which play important post-transcriptional regulatory roles in gene expression and can greatly influence viral replication and pathogenesis. Here, we employed deep sequencing technology to determine cellular miRNAs expression profile in goat peripheral blood mononuclear cells (PBMCs) infected with Nigeria 75/1 vaccine virus, a widely used vaccine strain for mass vaccination programs against Peste des petits ruminants (PPR). Expression analysis demonstrated that PPRV infection can elicit 316 significantly differentially expressed (DE) miRNAs including 103 known and 213 novel miRNAs candidates in infected PBMCs at 24 hours post-infection as compared with mock control. Target prediction and functional analysis of these DEmiRNAs revealed significant enrichment for several signaling pathways including TLR signaling pathways, PI3K-Akt, endocytosis, viral carcinogenesis, and JAK-STAT signaling pathways. This study provides a valuable basis for further investigation on the roles of miRNAs in PPRV replication and pathogenesis.
Project description:Peste des petits ruminants virus (PPRV) is the causative agent of peste des petits ruminants (PPR), a highly contagious disease in small ruminants that causes massive economic losses worldwide. Despite its impact, the mechanisms underlying PPRV infections remain elusive, hindering its control and prevention. This study examined the molecular mechanisms underlying PPRV infections by investigating the transcriptomic changes in PPRV-infected goat endometrial epithelial cells (EECs) and clarifying the regulatory role of the stimulator of interferon genes (STING) signaling pathway in PPRV replication. A total of 1946 DEGs (1,078 up-regulated and 868 down-regulated) were identifie in PPRV-infected EECs. GO and KEGG enrichment analysis showed that the DEGs were κB and tumor necrosis factor signaling pathways. Western blot analysis showed that PPRV promotes STING and p-TBK1 expression. Specifically, overexpression of STING significantl enhanced PPRV replication, while the knockdown of STING by specific siRNA markedly reduced STING protein expression and significantly decreased the PPRV-N protein levels and viral titer (TCID50) in Vero CCL-81 and glomerular microvascular endothelial cells.
Project description:Viruses have evolved numerous strategies to impair immunity so that they can replicate more efficiently, such as the immunosuppressive effects of Morbillivirus infection. In the present work we hypothesized that the highly contagious morbillivirus Peste des Petits Ruminants virus (PPRV) could target monocytes and dendritic cells (DC) to contribute to the immunosuppressive effects produced by the infection. Monocytes isolated from healthy sheep donor, a natural host of the disease, could be infected by PPRV and this impaired the differentiation and phagocytic ability of immature monocyte-derived DC (MoDC). Ovine MoDC could be productively infected by PPRV, and this drastically reduced MoDC capacity to activate allogeneic T cell responses. Transcriptomic analysis of infected MoDC indicated that several tolerogenic DC signature genes were upregulated upon PPRV infection.