miR-383 Regulates Hepatic Lipid Homeostasis and Response to Dengue Virus Infection.

Recently, microRNAs (miRNAs), as endogenous noncoding RNAs that inhibit mRNA translation, have been identified to broadly possess functional roles in regulating cellular signaling and metabolic processes due to their chemical and biological properties. In addition, they have emerged to be of critical importance in modulating host-virus interactions, especially for RNA viruses. Herein, we discovered that miR-383-5p targets certain lipid and cholesterol biosynthetic pathways and restricts Dengue virus (DENV) infection in hepatic cells. Global transcriptomics analysis of Huh7 human hepatoma cells overexpressing miR-383-5p revealed enrichment of lipid and cholesterol metabolic processes. Bioinformatics analysis of genes repressed in miR-383-5p overexpressing cells divulged the repression of a key target PLA2G4A, a pro-viral host factor essential for the production of infectious DENV particles. Our study demonstrated the effectiveness of miRNA mimics as tools to study cellular signaling pathways that contribute to viral pathogenesis. Overall, our study identifies miR-383-5p as an interesting host factor during DENV propagation and highlights a potential therapeutic role in the regulation of hepatic lipid metabolism and an antiviral response to DENV.