Gh. Lee et al., Dissociation of sarcoglycans and the dystrophin carboxyl terminus from thesarcolemma in enteroviral cardiomyopathy, CIRCUL RES, 87(6), 2000, pp. 489-495
Enteroviral infection can cause an acquired form of dilated cardiomyopathy.
We recently reported that dystrophin is cleaved, functionally impaired, an
d morphologically disrupted in vitro as well as in vivo during infection wi
th coxsackievirus B3, Genetic dystrophin truncations lead to a marked decre
ase in dystrophin-associated glycoproteins, whereas expression of only the
naturally occurring dystrophin carboxyl terminus, Dp-71, restores the sarco
lemmal association of the dystrophin-associated glycoproteins. We sought to
determine whether acute cleavage of dystrophin leads to a dissociation of
the carboxyl-terminal dystrophin fragment and of the sarcoglycans from the
sarcolemma during coxsackievirus B3 infection. We found that in cultured ca
rdiac myocytes and murine hearts infected with coxsackievirus B3, the sarco
lemmal localization of the dystrophin carboxyl terminus is lost. The dystro
phin-associated glycoproteins alpha-, beta-, gamma-, and delta-sarcoglycan
and beta-dystroglycan were markedly decreased in the membrane fraction of i
nfected cells in culture, and the typical sarcolemmal localization for each
of the se proteins was lost in coxsackievirus-B3-infected cardiomyocytes i
n vivo. Furthermore, sucrose gradient ultracentrifugation demonstrated that
delta-sarcoglycan was physically dissociated from dystrophin within the me
mbrane fraction. In vivo, the sarcolemmal integrity was functionally impair
ed with Evans blue dye uptake even though there was no generalized disrupti
on of the sarcolemma of infected myocytes evidenced by intact wheat germ ag
glutinin staining. In analogy to hereditary sarcoglycanopathies, this disin
tegration of the sarcoglycan complex may, in addition to the dystrophin cle
avage, play an important role in the pathogenesis of enterovirus-induced ca
rdiomyopathy. These results imply a potential role for disruption of the sa
rcoglycans in an acquired form of heart failure.