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RNA-seq Analysis of West Nile Virus Differential Pathogenicity

30 May 2016


RNA-seq technology was used to analyze host transcriptomes in the brains of mice experimentally infected with West Nile virus (WNV) NY99 (virulent strain) and WNV Eg101 (non-virulent strain) to gain insights into the underlying mechanisms of differential pathogenicity. Genes that were up-regulated in infection with both the viruses were mainly associated with interferon signaling. Genes associated with inflammation and cell death/apoptosis were only expressed with WNV NY99 infection. Differences in the activation of key pattern recognition receptors resulted in the induction of unique innate immune profiles, which corresponded with the induction of interferon and inflammatory responses. Pathway analysis of differentially expressed genes indicated that after WNV NY99 infection, TREM-1-mediated activation of Toll-like receptors leads to high inflammatory response. Differential expression of specific host genes observed between virulent and non-virulent WNV strains could explain the variation in disease pathogenicity. In conclusion, we have identified both common and specific responses to WNV NY99 and WNV Eg101 infections as well as genes linked to potential resistance to infection that may be targets for therapeutics.

Figure: WNV infection of the brain causes changes in cellular gene expression. Mice were infected with 100 PFU of PBS (Mock), WNV NY99 or WNV Eg101 by footpad route. At day 8 after infection, brains (n = 4 per group) were harvested. Bar graph showing the number and fold
change of up- and down-regulated genes.

Kumar M, Belcaid M, Nerurkar VR. Identification of host genes leading to West Nile virus encephalitis in mice brain using RNA-seq analysis. Scientific Reports 2016 May 23;6:26350. doi: 10.1038/srep26350.