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Comparative and temporal transcriptome analysis of peste des petits ruminants virus infected goat peripheral blood mononuclear cells

Manjunath, Siddappa, Mishra, Bishnu Prasad, Mishra, Bina, Sahoo, Aditya Prasad, Tiwari, Ashok K., Rajak, Kaushal Kishore, Muthuchelvan, D., Saxena, Shikha, Santra, Lakshman, Sahu, Amit Ranjan, Wani, Sajad Ahmad, Singh, R.P., Singh, Y.P., Pandey, Aruna, Kanchan, Sonam, Singh, R.K., Kumar, Gandham Ravi, Janga, Sarath Chandra
Virus research 2017 v.229 pp. 28-40
Peste-des-petits-ruminants virus, adaptive immunity, complement, cytokines, gene expression, gene expression regulation, genes, goats, immune response, inflammation, innate immunity, interferon regulatory factors, interferons, mononuclear leukocytes, peste des petits ruminants, quantitative polymerase chain reaction, reverse transcriptase polymerase chain reaction, sheep, signal transduction, temporal variation, transcriptomics, vaccination, vaccines, viruses, India
Peste des petits ruminanats virus (PPRV), a morbillivirus causes an acute, highly contagious disease – peste des petits ruminants (PPR), affecting goats and sheep. Sungri/96 vaccine strain is widely used for mass vaccination programs in India against PPR and is considered the most potent vaccine providing long-term immunity. However, occurrence of outbreaks due to emerging PPR viruses may be a challenge. In this study, the temporal dynamics of immune response in goat peripheral blood mononuclear cells (PBMCs) infected with Sungri/96 vaccine virus was investigated by transcriptome analysis. Infected goat PBMCs at 48h and 120h post infection revealed 2540 and 2000 differentially expressed genes (DEGs), respectively, on comparison with respective controls. Comparison of the infected samples revealed 1416 DEGs to be altered across time points. Functional analysis of DEGs reflected enrichment of TLR signaling pathways, innate immune response, inflammatory response, positive regulation of signal transduction and cytokine production. The upregulation of innate immune genes during early phase (between 2-5 days) viz. interferon regulatory factors (IRFs), tripartite motifs (TRIM) and several interferon stimulated genes (ISGs) in infected PBMCs and interactome analysis indicated induction of broad-spectrum anti-viral state. Several Transcription factors – IRF3, FOXO3 and SP1 that govern immune regulatory pathways were identified to co-regulate the DEGs. The results from this study, highlighted the involvement of both innate and adaptive immune systems with the enrichment of complement cascade observed at 120h p.i., suggestive of a link between innate and adaptive immune response. Based on the transcriptome analysis and qRT-PCR validation, an in vitro mechanism for the induction of ISGs by IRFs in an interferon independent manner to trigger a robust immune response was predicted in PPRV infection.