Japanese Encephalitis Virus infection increases USP42 to stabilize TRIM21 and OAS1 for neuroinflammatory and anti-viral response in human microglia

Abstract

Japanese Encephalitis Virus (JEV), a member virus of Flaviviridae family causes Japanese encephalitis (JE). JE is a mosquito-borne disease, spread mainly by Culex spp. During JE, dysregulated inflammatory responses play a central role in neuronal death and damage leading to Neuroinflammation. In this study, we show that JEV infection in human microglial cells (CHME3) reduces the cellular miR-590-3p levels. miR-590-3p could directly target the expression levels of USP42 (Ubiquitin Specific Peptidase 42) resulting in increased cellular levels of USP42 upon JEV infection. Our results suggest that USP42 stabilizes cellular TRIM21 via deubiquitinating them. We also established through various in vitro and in vivo experiments that increased USP42 can maintain a higher cellular level of both TRIM21 as well as OAS1. This study also suggests that TRIM21, independently of its RING domain, can increase USP42 level in a positive feedback loop and induces the cellular OAS1 levels in human microglial cells.