Type I interferon and MAVS signaling restricts chikungunya virus heart infection and cardiac tissue damage

Chikungunya virus (CHIKV) infection has been associated with severe cardiac manifestations. However, how CHIKV infection leads to heart disease remains unknown. Using C57BL/6 mice, we show that cardiac fibroblasts are the main target of CHIKV infection in the heart, and that cardiac tissue infection induces a local and robust type I interferon (IFN-I) response in both infected and non-infected cardiac cells. The loss of IFN-I signaling results in increased CHIKV infection, virus spreading, and apoptosis in cardiac tissue. Importantly, signaling through the mitochondrial antiviral-signaling protein (MAVS) is essential for efficient CHIKV clearance from the heart. Indeed, persistent infection in cardiac tissue of MAVS-deficient mice leads to cardiac damage characterized by focal myocarditis and major vessel vasculitis. This study provides a new mouse model of CHIKV cardiac infection and mechanistic insight on how CHIKV can lead to cardiac damage, underscoring the importance of monitoring cardiac function in patients with CHIKV infections. ### Competing Interest Statement The authors have declared no competing interest.