Laboratory of Virology, National Institute of Immunology, Aruna Asaf Ali Road, New Delhi, 110067, India.
National Brain Research Centre, Manesar, Haryana, 122052, India.
Virology. 2022 Aug;573:131-140. doi: 10.1016/j.virol.2022.06.012. Epub 2022 Jun 25.
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.
日本脑炎病毒（JEV）是黄病毒科的一种成员病毒，可引起日本脑炎（JE）。JE 是一种由库蚊属（Culex spp.）传播的蚊媒疾病。在 JE 中，失调的炎症反应在神经元死亡和损伤导致神经炎症中起核心作用。在这项研究中，我们表明 JEV 感染人小神经胶质细胞（CHME3）会降低细胞中 miR-590-3p 的水平。miR-590-3p 可以直接靶向 USP42（泛素特异性肽酶 42）的表达水平，导致 JEV 感染后细胞内 USP42 水平增加。我们的结果表明，USP42 通过去泛素化来稳定细胞中的 TRIM21。我们还通过各种体外和体内实验证实，增加的 USP42 可以维持更高的细胞水平的 TRIM21 和 OAS1。本研究还表明，TRIM21 可以独立于其 RING 结构域，在正反馈回路中增加 USP42 水平，并诱导人小神经胶质细胞中的细胞 OAS1 水平。
