Japanese Encephalitis Virus exploits microRNA-155 to suppress the non-canonical NF-κB pathway in human microglial cells

Abstract

Japanese Encephalitis Virus (JEV) is a single positive strand RNA virus, belongs to the Flaviviridae family. JEV is neurotropic in nature which accounts for 30–50% neurological, psychiatric sequelae and movement disorder, with 20–30% case fatality rate among children or elder population. JEV causes neuronal loss and microglial activation which leads to neuroinflammation. The microRNAs are the molecular switches, which regulate the gene expression post-transcriptionally. The microRNA-155 has been reported to be associated with CNS-related pathologies like, experimental autoimmune encephalitis, multiple sclerosis and amyotrophic lateral sclerosis. In the present study, we infected microglial cells with JEV, which resulted in the up-regulation of microRNA-155; quantified by real-time polymerase chain reaction. The gene target prediction databases revealed pellino 1 as a putative gene target for microRNA-155. The over-expression based studies of microRNA-155 mimics, scrambles, inhibitors, and cy3 negative control demonstrated the role of PELI1 in the regulation of the non-canonical NF-κB pathway via TRAF3. The luciferase assay showed the regulation of NF-κB promoter via microRNA-155 in JEV infected microglial cells. The suppression of NF-κB in JEV infected microglial cells led to the reduced expression of IL-6 and TNF-α. JEV exploits cellular microRNA-155 to suppress the expression of PELI1 in human microglial cells as a part of their immune evasion strategy.