Changes in m6A RNA methylation of goat lung following PPRV infection.

Peste des petits ruminants (PPR) is an acute, highly contagious viral disease of goats and sheep, caused by the Peste des petits ruminants virus (PPRV). Earlier studies suggest the involvement of diverse regulatory mechanisms in PPRV infection. Methylation at N6 of Adenosine called m6A is a type RNA modification that influences various physiological and pathological phenomena. As the lung tissue represents the primary target organ of PPRV, the present study explored the m6A changes and their functional significance in PPRV disease pathogenesis. m6A-seq analysis revealed 1289 m6A peaks to be significantly altered in PPRV infected lung in comparison to normal lung, out of which 975 m6A peaks were hypomethylated and 314 peaks were hypermethylated. Importantly, hypomethylated genes were enriched in Interleukin-4 and Interleukin-13 signaling and various processes associated with extracellular matrix organization. Further, of the 843 differentially m6A-containing cellular transcripts, 282 transcripts were also found to be differentially expressed. Functional analysis revealed that these 282 transcripts are significantly enriched in signaling by Interleukins, extracellular matrix organization, cytokine signaling in the immune system, signaling by receptor tyrosine kinases, and Toll-like Receptor Cascades. We also found m6A reader HNRNPC and the core component of methyltransferase complex METTL14 to be highly upregulated than the m6A readers - HNRNPA2B1 and YTHDF1 at the transcriptome level. These findings suggest that alteration in the m6A landscape following PPRV is implicated in diverse processes including Interleukin signaling.

Systems biology under heat stress in Indian cattle.

Transcriptome profiling of Vrindavani and Tharparkar cattle (n = 5 each) revealed that more numbers of genes were dysregulated in Vrindavani than in Tharparkar. A contrast in gene expression was observed with 18.9 % of upregulated genes in Vrindavani downregulated in Tharparkar and 17.8% upregulated genes in Tharparkar downregulated in Vrindavani. Functional annotation of genes differentially expressed in Tharparkar and Vrindavani revealed that the systems biology in Tharparkar is moving towards counteracting the effects due to heat stress. Unlike Vrindavani, Tharparkar is not only endowed with higher expression of the scavengers (UBE2G1, UBE2S, and UBE2H) of misfolded proteins but also with protectors (VCP, Serp1, and CALR) of naïve unfolded proteins. Further, higher expression of the antioxidants in Tharparkar enables it to cope up with higher levels of free radicals generated as a result of heat stress. In this study, we found relevant genes dysregulated in Tharparkar in the direction that can counter heat stress.

Contrasting Gene Expression Profiles of Monocytes and Lymphocytes From Peste-Des-Petits-Ruminants Virus Infected Goats.

In this study, transcriptome analysis of PPRV infected PBMC subsets-T helper cells, T cytotoxic cells, monocytes, and B lymphocytes was done to delineate their role in host response. PPRV was found to infect lymphocytes and not monocytes. The established receptor for PPRV-SLAM was found downregulated in lymphocytes and non-differentially expressed in monocytes. A profound deviation in the global gene expression profile with a large number of unique upregulated genes (851) and downregulated genes (605) was observed in monocytes in comparison to lymphocytes. ISGs-ISG15, Mx1, Mx2, RSAD2, IFIT3, and IFIT5 that play a role in antiviral response and the genes for viral sensors-MDA5, LGP2, and RIG1, were found to be upregulated in lymphocytes and downregulated in monocytes. The transcription factors-IRF-7 and STAT-1 that regulate expression of most of the ISGs were found activated in lymphocytes and not in monocytes. Interferon signaling pathway and RIG1 like receptor signaling pathway were found activated in lymphocytes and not in monocytes. This contrast in gene expression profiles and signaling pathways indicated the predominant role of lymphocytes in generating the antiviral response against PPRV in goats, thus, giving us new insights into host response to PPRV.