Here, we demonstrated: (i) that cardiac fibroblasts are a direct target of CHIKV infection in an immunocompetent host; (ii) that cardiac tissue elicits a local IFN-I response required for CHIKV clearance and preventing tissue damage; (iii) that in the absence of MAVS signaling CHIKV persists in infected hearts, and (iv) that failure to clear CHIKV in Mavs−/− mice leads to focal myocarditis and chronic large vessel vasculitis detectable up to 60 dpi. Here, MAVS is linked to Large vessel vasculitis.