Dystrophin deficiency markedly increases enterovirus-induced cardiomyopathy: a genetic predisposition to viral heart disease.
Both enteroviral infection of the heart and mutations in the dystrophin gene can cause cardiomyopathy. Little is known, however, about the interaction between genetic and acquired forms of cardiomyopathy. We previously demonstrated that the enteroviral protease 2A cleaves dystrophin; therefore, we hypothesized that dystrophin deficiency would predispose to enterovirus-induced cardiomyopathy. We observed more severe cardiomyopathy, worsening over time, and greater viral replication in dystrophin-deficient mice infected with enterovirus than in infected wild-type mice. This difference appears to be a result of more efficient release of the virus from dystrophin-deficient myocytes. In addition, we found that expression of wild-type dystrophin in cultured cells decreased the cytopathic effect of enteroviral infection and the release of virus from the cell. We also found that expression of a cleavage-resistant mutant dystrophin further inhibited the virally mediated cytopathic effect and viral release. These results indicate that viral infection can influence the severity and penetrance of the cardiomyopathy that occurs in the hearts of dystrophin-deficient individuals.
Department of Medicine, Institute of Molecular Medicine and The Cardiovascular Center, University of California, San Diego, California, USA.
Dingding
D
Xiong
Gil-Hwan
GH
Lee
Cornel
C
Badorff
Andrea
A
Dorner
Sang
S
Lee
Paul
P
Wolf
Kirk U
KU
Knowlton
D000818:Animals; D016466:CHO Cells; D009202:Cardiomyopathies / Q000235:genetics* / Q000503:physiopathology / Q000821:virology*; D002460:Cell Line; D006224:Cricetinae; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D004770:Enterovirus / Q000502:physiology; D004769:Enterovirus Infections / Q000503:physiopathology* / Q000821:virology; D005260:Female; D020022:Genetic Predisposition to Disease; D049452:Green Fluorescent Proteins; D006321:Heart / Q000821:virology*; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018101:Mice, Inbred mdx; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D010375:Pedigree; D012508:Sarcolemma / Q000378:metabolism / Q000473:pathology
D016189:Dystrophin; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins