In silico and in vivo studies reveal that Theiler's murine encephalomyelitis virus induces upregulation of miR-155-5p in the hippocampus.

Abstract

MicroRNAs (miRNAs) are perceived as master regulators of gene expression in the cells. Their involvement has been demonstrated in the etiopathogenesis of many neurological disorders, including central nervous system (CNS) infection, neuroinflammation, seizures and epilepsy. Here, we evaluated the role of miRNAs in the Theiler's murine encephalomyelitis virus (TMEV) model. Using in silico modeling, we indicated miRNAs potentially associated with the regulation of the largest number of differentially expressed (DE) genes in the TMEV model. Next, we developed TMEV model with a tissue collection at Days 7 and 10 post infection (PI). We performed qPCR to identify the miRNAs of interest. Finally, we conducted bioinformatic analyses of the affected miRNAs to characterize biological processes and the most significant interactions among DE genes. The expression of miR-155-5p was significantly increased in the hippocampi of the TMEV-infected mice at Days 7 and 10 PI, showing approximately 60-fold upregulation. We also observed enhanced expression of miR-17-5p in response to viral infection at both Days 7 and 10 PI. The expression of miR-34a-5p and miR-15a-5p was elevated at Day 10 PI. Enrichment analysis associated miR-155-5p and miR-17-5p pathways with apoptosis, microglial activity regulator TYROBP (tyrosine kinase binding protein), interleukin 2 and 5 signaling. Among downregulated miR-155-5p targets, interleukin 1β was identified as gene with the highest number of interactions with other DE genes. Our findings indicate that miR-155-5p and its targets, are promising candidates for future functional studies aimed to improving both, treatment and diagnosis of virus-induced complications like seizures.