A recombinant CHIKV-NLuc virus identifies chondrocytes as target of Chikungunya virus in a immunocompetent mouse model

Abstract

AbstractFirst isolated in 1953 in Tanzania, the arthritogenic Chikungunya virus (CHIKV) re-emerged globally in 2005, leading to widespread outbreaks. Unlike other arboviruses, CHIKV predominantly induces symptomatic infections (72-96%), marked by fever, myalgia, polyarthralgia, and rash. Although rarely fatal, atypical forms such as encephalopathies can occur. Notably, 75.4% of patients experience persistent arthralgias for up to three years after the acute phase. Understanding CHIKV’s pathophysiology in the joints is challenging due to the difficulties to obtain biological samples. The study employs a mouse model infected with a reporter virus expressing a Nano Luciferase to investigate the disease’s transition to chronic arthritis. The murine model reveals viral replication in metatarsi joints, particularly in chondrocytes, confirmed in primary human chondrocytes undergoing viral-induced apoptosis.Ex vivoanalysis confirmed viral replication in leg bones and articular cartilages, with histological evidence of focal erosive lesions and periarticular inflammation. The study further utilizes anin vivoimaging mouse model to monitor viral replication over time. Human chondrocytes prove susceptible to CHIKV infection, exhibiting active viral replication, bioluminescence activity, and increased viral production. CHIKV induced apoptosis, the upregulation of markers associated with cartilage remodeling and altered the cytokine production. This comprehensive study, utilizing advanced techniques and models, provides insights into CHIKV’s ability to infect articular cartilages, shedding light on the mechanisms of chronic arthritis following infection.