IFNAR signalling and cardiac mitochondrial function in SARS-CoV-2 infection

https://doi.org/10.1007/s00392-024-02526-y

Carina Gross (Hannover)1, L. M. Busker (Hannover)2, A. Pavlou (Hannover)2, M. Obara (Hannover)2, M. Bruhn (Hannover)2, S. Clever (Hannover)3, C. Meyer zu Natrup (Hannover)3, I. Zdora (Hannover)4, F. Moeselaken (Hannover)4, K. Hülskötter (Hannover)4, T. Störk (Hannover)4, M. von Köckritz-Blickwede (Hannover)5, S. Perlman (Iowa City)6, A. Volz (Hannover)3, W. Baumgärtner (Hannover)4, J. Bauersachs (Hannover)1, U. Kalinke (Hannover)2, G. Amanakis (Hannover)1

1Medizinische Hochschule Hannover Kardiologie und Angiologie Hannover, Deutschland; 2TWINCORE Centre for Experimental and Clinical Infection Research Hannover, Deutschland; 3University of Veterinary Medicine Hannover Institute of Virology Hannover, Deutschland; 4University of Veterinary Medicine Hannover Department of Pathology Hannover, Deutschland; 5University of Veterinary Medicine Hannover Research Center for Emerging Infections and Zoonoses Hannover, Deutschland; 6Carver College of Medicine Department of Microbiology and Immunology Iowa City, USA

 

COVID19 still poses an unmet need in healthcare systems, causing severe disease in the elderly and in immunocompromised individuals. Cardiac involvement in COVID19, in terms of myocarditis and Troponin release is associated with higher mortality. Similar to other RNA cardiotropic viruses, we hypothesized that defects in type I interferon axis cause inability to control SARS-CoV-2 infection and severe disease. To test this hypothesis, we infected wild type C57BL/6 mice (WT) and mice lacking the type I interferon receptor (IFNAR -/-) with a mouse-adapted SARS-CoV-2 strain. IFNAR -/- mice exhibited a milder progress of the infection as well as less calcium-induced mitochondrial swelling in cardiac tissue than WT mice, indicating that 1) type I interferon axis contributes to controlling SARS-CoV-2 infection in mice and 2) there is a possible cross-talk between type I interferon signalling and cardiac mitochondrial function.

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