ABSTRACT Chikungunya virus (CHIKV) infection has been associated with severe cardiac manifestations, yet, how CHIKV infection leads to heart disease remains unknown. Here, we leveraged both mouse models and human primary cells to define the mechanisms of CHIKV heart infection. We found that CHIKV actively replicates in cardiac fibroblasts and is cleared without significant tissue damage through the induction of a local type-I interferon response from both infected and non-infected cardiac cells. Importantly, signaling through the mitochondrial antiviral-signaling protein (MAVS) is required for viral clearance from the heart. In the absence of MAVS, persistent infection leads to focal myocarditis and major vessel vasculitis persisting for up to 60 days post-infection, suggesting CHIKV can lead to vascular inflammation and potential long-lasting cardiovascular complications. This study provides a model of CHIKV cardiac infection and mechanistic insight into CHIKV-induced heart disease, underscoring the importance of monitoring cardiac function in patients with CHIKV infections.

MAVS signaling is required for clearance of chikungunya heart infection and prevention of chronic inflammation in vascular tissue