From Infection to Inflammation: A Transcriptome-Wide Analysis of CHIKV Impact on Primary Human Skeletal Muscle Cells

Abstract Chikungunya virus (CHIKV) is a single-stranded RNA virus belonging to the Togaviridae family and Alphavirus genus. It causes chikungunya fever, transmitted by Aedes mosquitoes, and is characterized by severe fever, joint pain, rash, headaches, and muscle pain lasting days to weeks. In some cases, chronic arthritis resembling rheumatoid arthritis can develop post-infection. Currently, there's no specific antiviral treatment for CHIKV, with supportive care being the main treatment approach. Chronic arthritis management includes pain relief and preventing joint damage with NSAIDs, among other medications. The role of inflammatory cytokines and chemokines in CHIKV infection, which contribute to symptom severity, parallels inflammatory arthritis, suggesting shared pathology. Our study used human primary muscle cells to explore CHIKV infection and its effects, observing a rise in proinflammatory cytokines 24 hours post-infection. This supports the connection between CHIKV infection and arthritis symptoms. The research established these cells as susceptible to CHIKV, with peak viral levels at 24 hours post-infection. RNA sequencing (RNA-Seq) was employed to analyze gene expression changes due to CHIKV, revealing gene alterations associated with skeletal and muscle disorders, immune response, cell growth and death, and viral replication. This study enhances understanding of CHIKV's pathogenic mechanisms using a clinically relevant human cell model, providing the groundwork for future research into CHIKV’s interactions with host cells during different infection stages.