Use of Recombinant Chikungunya Virus expressing Nanoluciferase to Identify Chondrocytes as Target Cells in an Immunocompetent Mouse Model.

Abstract

Chikungunya virus (CHIKV) induces predominantly symptomatic infections, marked by fever, myalgia, rash and polyarthralgia that can last for up to 3 years after infection. Understanding the pathophysiology of CHIKV in the joints is challenging due to limited access to biological samples. Using a reporter virus expressing Nanoluciferase in a mouse model allowed us to monitor viral replication in real-time during acute and postacute phases. We showed viral replication in chondrocyte containing tissue in the metatarsi joints and confirmed with ex vivo analyses viral replication in leg bones and articular cartilages with histological evidence of focal erosive lesions and periarticular inflammation. Moreover, human chondrocytes prove susceptible to CHIKV infection, exhibiting viral production and bioluminescence activity. CHIKV induced apoptosis, the up-regulation of markers associated with cartilage remodeling and altered cytokine production. Our study provides insights into the ability of CHIKV to infect articular cartilages, shedding light on the mechanisms of alphaviral arthritis.