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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, yet, how CHIKV infection leads to heart disease remains unknown. Here, we leveraged both mouse models and human primary cardiac cells to define the mechanisms of CHIKV heart infection. Using an immunocompetent mouse model of CHIKV infection as well as human primary cardiac cells, we demonstrate that CHIKV directly infects and actively replicates in cardiac fibroblasts. In immunocompetent mice, CHIKV is cleared from cardiac tissue without significant damage through the induction of a local type I interferon response from both infected and non-infected cardiac cells. Using mice deficient in major innate immunity signaling components, we found that signaling through the mitochondrial antiviral-signaling protein (MAVS) is required for viral clearance from the heart. In the absence of MAVS signaling, persistent infection leads to focal myocarditis and vasculitis of the large vessels attached to the base of the heart. Large vessel vasculitis was observed 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.

SUBMITTER: Noval MG

PROVIDER: S-EPMC10400619 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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

Noval Maria G MG Spector Sophie N SN Bartnicki Eric E Izzo Franco F Narula Navneet N Yeung Stephen T ST Damani-Yokota Payal P Dewan M Zahidunnabi MZ Mezzano Valeria V Rodriguez-Rodriguez Bruno A BA Loomis Cynthia C Khanna Kamal M KM Stapleford Kenneth A KA

Nature communications 20230803 1

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 cardiac cells to define the mechanisms of CHIKV heart infection. Using an immunocompetent mouse model of CHIKV infection as well as human primary cardiac cells, we demonstrate that CHIKV directly infects and actively replicates in cardiac fibroblasts. In immunocompetent mice, CHIKV is cl ...[more]

PMID: 37537212

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

Publications

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

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