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MAVS signaling is required for preventing persistent chikungunya heart infection and chronic vascular tissue inflammation

ABSTRACT: Chikungunya virus (CHIKV) infection has been associated with severe cardiac manifestations. However, how CHIKV infection leads to heart disease remains unknown. Here, 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 activation of the type I interferon (IFN-I) pathway 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 mechanistic insight on how CHIKV can lead to cardiac damage, underscoring the importance of monitoring cardiac function in patients with CHIKV infections.

ORGANISM(S): Mus musculus

PROVIDER: GSE204689 | GEO | 2023/06/10

REPOSITORIES: GEO

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