Research Projects

The Chikungunya virus (CHIKV), an alphavirus that is transmitted by mosquitoes, induces an acute febrile illness that frequently develops into chronic polyarthritis, which can endure for months or even years. Sustained elevation of Interleukin-6 (IL-6), a pleiotropic cytokine that is involved in synovial inflammation, osteoclast activation, and joint degradation, is a critical pathological characteristic of CHIKV-induced arthritis. Although IL-6 is essential for the early stages of antiviral responses, its continued expression following viral clearance is strongly associated with the development of chronic joint inflammation. The post-transcriptional mechanisms that maintain IL-6 signaling during the chronic phase of CHIKV infection are not well understood, despite the fact that its transcriptional regulation has been thoroughly characterized. New evidence indicates that microRNAs (miRNAs) play a critical role in the regulation of inflammatory signaling. In particular, miRNAs such as miR-155, miR-146a, and miR-223 are recognized for their ability to target critical modulators of the IL-6 pathway, including IL-6R, gp130, JAK1, STAT3, and the negative regulators SOCS1 and SOCS3. In other disease contexts, these miRNAs have been demonstrated to regulate macrophage activation and maintain pro-inflammatory signaling; however, their function in macrophages infected with CHIKV is still unexplored. This project proposes that CHIKV infection upregulates specific inflammation-associated miRNAs in macrophages, thereby sustaining IL-6 signaling by repressing feedback inhibitors and promoting STAT3 activation. In order to address this issue, the study will employ qRT-PCR to identify differentially expressed miRNAs in CHIKV-infected THP-1-derived macrophages. Subsequently, functional validation will be achieved through the transfection of miRNA mimics and inhibitors. qRT-PCR, Western blotting, and immunocytochemistry will be employed to evaluate the impact on IL-6 pathway components at both the transcript and protein levels. Simultaneously, plant-derived flavonoids with reported anti-inflammatory and miRNA-modulatory activities will be evaluated via in silico docking against IL-6 pathway proteins and subsequently validated in vitro for their capacity to modulate miRNA expression and restore homeostatic signaling. Through the combination of miRNA selection and small-molecule screening, this research seeks to identify new IL-6 regulation mechanisms in CHIKV pathogenesis and investigate flavonoid-based approaches to immunological balance restoration. The results have a significant translational potential for the development of affordable, plant-based therapeutics for CHIKV-associated arthritis, a pressing need in endemic regions like India. More broadly, this research will improve our comprehension of miRNA-mediated inflammation in chronic viral diseases and contribute to host-directed therapeutic approaches