Coxsackievirus B3 modulates cardiac ion channels

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Katja SteinkeGuiscard Seebohm

Abstract

Infections with coxsackieviruses of type B (CVBs), which are known to induce severe forms of acute and chronic myocarditis, are often accompanied by ventricular arrhythmias and sudden cardiac death. The mechanisms underlying the development of virus-induced, life-threatening arrhythmias, which are phenotypically similar to those observed in patients having functionally impaired cardiac ion channels, remain, however, enigmatic. In the present study, we show, for the first time, modulating time-dependent effects of CVB3 on the cardiac ion channels KCNQ1, hERG1, and Cav1.2 in heterologous expression. Channel protein abundance in cellular plasma membrane and patterns of their subcellular distribution were altered in infected murine hearts. The antiviral compound AG7088 did not prevent these effects on channels. In silico analyses of infected human myocytes suggest pronounced alterations of electrical and calcium signaling and increased risk of arrhythmogenesis. These modifications are attenuated by the common Asian polymorphism KCNQ1 P448R, a genetic determinant preventing coxsackievirus-induced effects in vitro. This study provides a previously unknown explanation for the development of arrhythmias in enteroviral myocarditis, whic...Continue Reading

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Citations

Nov 8, 2015·Biochemistry. Biokhimii︠a︡·Xia ZhaiZhaohua Zhong
Oct 28, 2016·Virchows Archiv : an International Journal of Pathology·Nicole Ettischer-SchmidKarin Klingel
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Oct 14, 2020·Nature Reviews. Cardiology·Carsten TschöpeSophie Van Linthout

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