Chikungunya Virus Infection Alters Expression of MicroRNAs Involved in Cellular Proliferation, Immune Response and Apoptosis

Abstract

Objective(s): Chikungunya virus (CHIKV) is a reemerging virus of significant importance that has caused large-scale outbreaks in the countries with a temperate climate. CHIKV causes debilitating arthralgia which can persist for weeks and up to a year. Fibroblast cells are the main target of CHIKV infection. In this study, we analyzed microRNA (miRNA) modulation in the fibroblast cells infected with CHIKV at an early stage of infection. Methods: 760 miRNAs were analyzed for modulation following infection with CHIKV at 6 h after infection. Bioinformatic analysis was done to identify the signaling pathway that may be targeted by the significantly modulated miRNAs. Validation of the miRNAs was done using a singleplex miRNA assay and protein target validation of modulated miRNAs was done by Western blot analysis. Results: Computational analysis of the significantly modulated miRNAs indicated their involvement in signaling pathways such as Toll-like receptor, mTOR, JAK-STAT and Pi3-Akt pathways, which have been shown to play important roles during CHIKV infection. Topoisomerase IIβ, a target of two of the modulated miRNAs, was downregulated upon CHIKV infection. Conclusion(s): We identified several miRNAs that may play important roles in early events after CHIKV infection and can be potential therapeutic targets against CHIKV infection.