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

Maria G. Noval (), Sophie N. Spector, Eric Bartnicki, Franco Izzo, Navneet Narula, Stephen T. Yeung, Payal Damani-Yokota, M. Zahidunnabi Dewan, Valeria Mezzano, Bruno A. Rodriguez-Rodriguez, Cynthia Loomis, Kamal M. Khanna and Kenneth A. Stapleford ()
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Maria G. Noval: New York University Grossman School of Medicine
Sophie N. Spector: New York University Grossman School of Medicine
Eric Bartnicki: New York University Grossman School of Medicine
Franco Izzo: New York Genome Center
Navneet Narula: New York University Grossman School of Medicine
Stephen T. Yeung: New York University Grossman School of Medicine
Payal Damani-Yokota: New York University Grossman School of Medicine
M. Zahidunnabi Dewan: New York University Grossman School of Medicine
Valeria Mezzano: New York University Grossman School of Medicine
Bruno A. Rodriguez-Rodriguez: New York University Grossman School of Medicine
Cynthia Loomis: New York University Grossman School of Medicine
Kamal M. Khanna: New York University Grossman School of Medicine
Kenneth A. Stapleford: New York University Grossman School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40047-w

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