C. Badorff et al., Enteroviral protease 2A cleaves dystrophin: Evidence of cytoskeletal disruption in an acquired cardiomyopathy, NAT MED, 5(3), 1999, pp. 320-326
Citations number
45
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Enteroviruses such as Coxsackievirus B3 can cause dilated cardiomyopathy, b
ut the mechanism of this pathology is unknown. Mutations in cytoskeletal pr
oteins such as dystrophin cause hereditary dilated cardiomyopathy, but it i
s unclear if similar mechanisms underlie acquired forms of heart failure. W
e demonstrate here that purified Coxsackievirus protease 2A cleaves dystrop
hin in vitro as predicted by computer analysis. Dystrophin is also cleaved
during Coxsackievirus infection of cultured myocytes and in infected mouse
hearts, leading to impaired dystrophin function. In vivo, dystrophin and th
e dystrophin-associated glycoproteins alpha-sarcoglycan and beta-dystroglyc
an are morphologically disrupted in infected myocytes. We suggest a molecul
ar mechanism through which enteroviral infection contributes to the pathoge
nesis of acquired forms of dilated cardiomyopathy.