Cardiac deletion of the coxsackievirus-adenovirus receptor abolishes coxsackievirus b3 infection and prevents myocarditis in vivo

Item Type:	Article
Title:	Cardiac deletion of the coxsackievirus-adenovirus receptor abolishes coxsackievirus b3 infection and prevents myocarditis in vivo
Creators Name:	Shi, Y. and Chen, C. and Lisewski, U. and Wrackmeyer, U. and Radke, M. and Westermann, D. and Sauter, M. and Tschoepe, C. and Poller, W. and Klingel, K. and Gotthardt, M.
Abstract:	OBJECTIVES: We investigated the role of the Coxsackievirus-adenovirus receptor (CAR) in viral myocarditis. BACKGROUND: CAR is involved in virus uptake into various cell types. It has therefore been suggested as a therapeutic target to prevent or treat Coxsackievirus B3 (CVB3)-induced diseases such as myocarditis and cardiomyopathy. Recent work in CAR-deficient animals has indicated a role in embryonic development and remodeling with cardiac malformation and lethality. METHODS: We generated a tamoxifen-inducible knockout (KO) mouse to study CAR in the adult heart after CVB3 infection. Histomorphology, virus distribution, and cardiac function were compared in CAR-KO versus noninduced littermate control animals expressing wild-type CAR (WT). RESULTS: We have demonstrated that eliminating CAR prevents signs of inflammatory cardiomyopathy, with essentially no pathology in KO hearts. Unlike CVB3-infected WT control animals, the cardiac inducible KO mice did not exhibit structural changes such as monocyte infiltration or fibrosis after CVB3 infection or increased production of markers of inflammation such as interleukin-6 and -10. Whereas CVB3 infection resulted in severe contractile dysfunction in the hearts of animals that express WT, the CAR-deficient hearts appeared normal. CONCLUSIONS: Elimination of CAR in adult hearts can efficiently block virus entry and the associated pathology including contractile dysfunction. The lack of infiltration or other morphological changes in CVB3-infected KO hearts emphasizes the contribution of direct virus-mediated pathology in enteroviral myocarditis.
Keywords:	Cell Adhesion Molecules, Myocarditis, Receptors, Viruses, Coxsackievirus Infections, Cytoplasmic and Nuclear Receptors, Transcription Factors, Animals, Mice
Source:	Journal of the American College of Cardiology
ISSN:	0735-1097
Publisher:	Elsevier
Volume:	53
Number:	14
Page Range:	1219-1226
Date:	7 April 2009
Official Publication:	https://doi.org/10.1016/j.jacc.2008.10.064
PubMed:	View item in PubMed

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