Modulation of Host miRNAs Transcriptome in Lung and Spleen of Peste des Petits Ruminants Virus Infected Sheep and Goats

Abstract

Peste des petits ruminants (PPR) is one of the highly contagious viral disease, characterized by fever, sore mouth, conjunctivitis, gastroenteritis, and pneumonia, primarily affecting sheep and goats. Reports suggested variable host response in goats and sheep and this host response vis-a-vis the expression of microRNAs (miRNAs) has not been investigated. Here, miRNAs were sequenced and proteomics data were generated to identify the role of differentially expressed miRNA (DEmiRNA) in PPR virus (PPRV) infected lung and spleen tissues of sheep and goats. In lungs, 67 and 37 DEmiRNAs have been identified in goats and sheep, respectively. Similarly, in spleen, 50 and 56 DEmiRNAs were identified in goats and sheep, respectively. A total of 20 and 11 miRNAs were found to be common differentially expressed in both the species in PPRV infected spleen and lung, respectively. Six DEmiRNAs—miR-21-3p, miR-1246, miR-27a-5p, miR-760-3p, miR-320a, and miR-363 were selected based on their role in viral infections, apoptosis, and fold change. The target prediction analysis of these six selected DEmiRNAs from the proteome data generated, revealed involvement of more number of genes in lung and spleen of goats than in sheep. On gene ontology analysis of host target genes these DEmiRNAs were found to regulate several immune response signaling pathways. It was observed that the pathways viz. T cell receptor signaling, Rap1 signaling, Toll-like receptor signaling, and B cell receptor signaling governed by DEmiRNAs were more perturbed in goats than in sheep. The data suggests that PPRV-induced miR-21-3p, miR-320a, and miR-363 might act cooperatively to enhance viral pathogenesis in the lung and spleen of sheep by downregulating several immune response genes. The study gives an important insight into the molecular pathogenesis of PPR by identifying that the PPRV—Izatnagar/94 isolate elicits a strong host response in goats than in sheep.

MicroRNA expression profiling of goat peripheral blood mononuclear cells in response to peste des petits ruminants virus infection

“…Emerging data have identified an important contribution of miRNA to the regulation of innate immune systems [ 41 , 42 ]. Here, PPRV infection in goat PBMC triggered the expression of many immune-related miRNA, including miR-150, miR-146, and let-7 family as previously observed in spleen and lung tissues of goats infected with PPRV [ 43 ]. Furthermore, 15 miRNA were identified from the 316 DEmiRNA co-expressed in two groups based on fold change values and their targeted gene roles in viral infection, antiviral response and apoptosis.…”

MicroRNA-1 Negatively Regulates Peripheral NK Cell Function via Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Signaling Pathways During PPRV Infection

“…MicroRNAs have been reported to regulate the innate and acquired immune responses, as well as the differentiation and development of immune cells. A growing number of reports suggest that virus infection, including PPRV, can alter cellular miRNA expression profile and thereby regulate host or viral RNA targets (50)(51)(52). Recently, our group has identified 103 known and 213 novel miRNAs from PPRV-infected goat PBMCs by using small RNA deep sequencing (27).…”

Transcriptional Profiles of Murine Bone Marrow-Derived Dendritic Cells in Response to Peste des Petits Ruminants Virus

“…These functions and associated metabolic pathways provide an immunological basis for understanding the impact on the maturation and differentiation of BMDCs. In particular, other DEGs related to immunity regulation or viral infection need to be further investigated [40]. Based on bioinformatics analysis, mRNA levels represent an intermediate state between gene expression and protein expression.…”