West Nile Virus inhibits type I interferon response via TRIM71 in human microglial cells.

West Nile Virus (WNV) is a mosquito-borne, single-stranded, positive-sense RNA virus of the Flaviviridae family. WNV infection may lead to meningitis and encephalitis. The type I interferon (IFN) response is the first line of host defense against viral infections. Viruses are reported to have evolved multiple strategies to suppress the type I IFN response to enhance viral replication and immune evasion. The tripartite motif-containing proteins (TRIMs) are reported to regulate antiviral immune responses during viral infections. However, the involvement of TRIM proteins and their underlying mechanism in WNV infection is poorly understood. In this study, we reported the TRIM71-mediated regulation of type I IFN in WNV-infected human microglial cells. WNV infection inhibits TRIM71, an E3 ubiquitin ligase in the TRIM family, in human microglial cells. Reduced TRIM71 levels led to increased AGO2 expression and downregulation of STING, resulting in decreased type-I IFN response in WNV-infected human microglial cells. Moreover, TRIM71 overexpression inhibited AGO2 and activated STING, thereby restoring IFNα/β production. The study suggests that WNV modulates the cellular machinery by inhibiting TRIM71, thereby suppressing the type I IFN response in human microglial cells.