Disruption of Dystrophin in Acute Fulminant Coxsackieviral B4 Infection
One mechanism that contributes to the pathogenesis of coxsackievirus B (CVB) viral heart disease is the direct cytopathic effect(s) on cardiomyocytes. It has been shown in mice that during CVB infection, the enteroviral protease 2A directly cleaves dystrophin in the hinge 3 region, leading to disruption of the dystrophin-glycoprotein complex and the loss of sarcolemmal integrity.1–3 We report for the first time a patient with fulminant myocarditis4 with CVB4 infection in which myocardial biopsy specimens demonstrated that there was disruption of the sarcolemmal localization of dystrophin in the same cells that were infected with CVB.
A 57-year-old woman was admitted with anterior chest pain for 1 day. Three days earlier, she experienced flu-like symptoms. The patient had elevated levels of troponin I (49.97 ng/mL) and creatinine phosphokinase-MB (98.27 ng/mL). A coronary angiogram showed no thrombus and no significant stenosis. Mechanical circulatory support was started with a left ventricular assist device (ECMO) because of progressive shock, pulmonary edema, and recurrent ventricular tachycardia. After 96 hours of support with ECMO, left ventricular wall motion was restored. The titers of the neutralizing CVB4 antibody changed from 1:16 (day 5) to 1:64 (day 16). Serial histological and immunohistochemical analyses of the left atrial appendage, which underwent biopsy at the time of insertion and removal of ECMO, showed the enteroviral capsid protein VP15 (NCL-ENTERO, Novocastra Laboratories) over the entire left atrial wall (Figure, A and B), with scanty inflammation infiltrates (Figure, C). The focal areas of myocardium displayed a loss of the sarcolemmal staining pattern for dystrophin using antidystrophin Ab (NCL-DYSA) that colocalized with enteroviral capsid proteins. (Figure, D) These findings demonstrate that in human coxsackievirus B myocarditis, a focal disruption of the dystrophin-glycoprotein complex can principally occur in patients with coxsackieviral myocarditis and may contribute to the pathogenesis of acute human enterovirus-induced myocardial infection.