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Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex
C Badorff1, G H Lee, K U Knowlton
1Department of Medicine, University of California, San Diego, USA.
Insights
Enteroviruses, like coxsackievirus B3, can cause dilated cardiomyopathy by cleaving dystrophin, a key protein. This impairs the dystrophin-glycoprotein complex, leading to heart muscle damage and dilated cardiomyopathy.
Area of Science:
- Cardiology
- Virology
- Molecular Biology
Background:
- Genetic defects in the dystrophin-glycoprotein complex are linked to hereditary dilated cardiomyopathy.
- Enteroviruses are known etiological agents of cardiomyopathy.
- A molecular mechanism linking enteroviruses to dilated cardiomyopathy has been proposed.
Purpose of the Study:
- To discuss the role of dystrophin cleavage in enterovirus-induced dilated cardiomyopathy.
- To explore the disruption of the dystrophin-glycoprotein complex during coxsackieviral infection.
- To elucidate the contribution of dystrophin cleavage to sarcolemmal permeability and heart muscle dysfunction.
Main Methods:
- Review of existing literature on enteroviruses, dystrophin, and cardiomyopathy.
- Analysis of the function of coxsackieviral protease 2A in dystrophin cleavage.
- Discussion of experimental evidence regarding sarcolemmal integrity loss during coxsackievirus B3 infection.
Main Results:
- Coxsackieviral protease 2A proteolytically cleaves and impairs dystrophin function.
- Infection with coxsackievirus B3 leads to disruption of the dystrophin-glycoprotein complex.
- Sarcolemmal integrity is compromised during coxsackieviral infection, increasing permeability.
Conclusions:
- Dystrophin cleavage is a critical factor in the development of enterovirus-induced dilated cardiomyopathy.
- Impaired dystrophin function and sarcolemmal disruption contribute to heart muscle pathology.
- Understanding these mechanisms may reveal therapeutic targets for viral cardiomyopathy.
Abstract:
Genetic deficiency of the dystrophin-glycoprotein complex causes hereditary dilated cardiomyopathy. Enteroviruses can also cause cardiomyopathy and we have recently described a potential molecular mechanism for enterovirus-induced dilated cardiomyopathy. The coxsackieviral protease 2A proteolytically cleaves and functionally impairs dystrophin. Additionally, during infection with coxsackievirus B3, the dystrophin-glycoprotein complex becomes disrupted and the sarcolemmal integrity is lost. This review article discusses the importance of the dystrophin cleavage for the development of increased sarcolemmal permeability and potential pathways for mechanisms by which the dystrophin cleavage during coxsackieviral infection may contribute to dilated cardiomyopathy.