Dynamic Interplay Between miR-133a and RBMX During Dengue Virus Infection

Viruses are obligate intracellular pathogens with limited genome capacity, relying entirely on host factors and cellular machinery for sustainable infection. In the present study, we demonstrate that dengue infection modulates the expression of RBMX (an RNA-binding protein) and miR-133a. Viral infection elevates the expression of the RBMX gene while downregulates the level of miR-133a. Additionally, Targetscan tool analysis shows that miR-133a possesses a potential binding site in the 3'UTR region of the RBMX gene, and our luciferase data indicate the miR-133a-mediated regulation of RBMX expression. Intriguingly, our time point study in Huh7 cells overexpressing the synthetic form of miR-133a mimic and inhibitor indicates the convoluted interaction between miR-133a and RBMX regulation during DENV infection. After 24 h postinfection (hpi), miR-133a significantly suppresses both the RBMX expression and viral RNA levels, acting as an antiviral agent by targeting the expression of the RBMX gene. Additionally, our immunoprecipitation result suggested the central role of DENV 3'UTR in regulating the expression of both RBMX and miR-133a. Furthermore, our study on RBMX Overexpression illuminates the vital function of RBMX protein in the DENV life cycle. Overexpression of the RBMX gene in ivermectin-pretreated cells partially rescues viral replication. This comprehensive study explicates the dynamic miRNA/RBPs regulatory axis during DENV pathogenesis.