Proapoptotic protein Siva binds to the muscle protein telethonin in cardiomyocytes during coxsackieviral infection.
OBJECTIVE
Coxsackievirus B3 (CVB3) is known to cause a variety of human diseases including acute and chronic myocarditis as well as dilated cardiomyopathy (DCM). However, the mechanisms by which CVB3 causes diseases are not well understood.


RESULTS
Studies identifying protein-protein interactions during CVB3 infection are useful in delineating the pathogenesis of acute or chronic myocarditis. Screening a human heart cDNA library revealed a yet unknown interaction partner of the proapoptotic protein Siva. We demonstrate that Siva specifically interacts with the heart and skeletal muscle protein telethonin. The expression of Siva is increased in heart tissue of CVB3-infected mice and the proteins colocalize in cardiomyocytes.


CONCLUSIONS
telethonin might be involved in CVB3-mediated cell damage and in the resulting cardiac dysfunction due to the interaction with Siva. We suggest a molecular mechanism through which coxsackieviral infection contributes to the pathogenesis of chronic myocarditis and in particular of acquired forms of DCM.
Department of Cell and Molecular Biology, Leibniz Institute for Natural Product Research and Infection Biology e. V. - Hans Knöll Institute, Beutenbergstr. 11a, D-07745 Jena, Germany.
Katharina
K
Mihatsch
Matthias
M
Nestler
Hans-Peter
HP
Saluz
Andreas
A
Henke
Thomas
T
Munder
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D064211:Connectin; D003384:Coxsackievirus Infections / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D010957:Plasmids; D011485:Protein Binding; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; D064211:Connectin; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C106549:SIVA1 protein, human; C577292:TCAP protein, human