Enteroviral
infection can cause an acquired form of
dilated cardiomyopathy. We recently reported that
dystrophin is cleaved, functionally impaired, and morphologically disrupted in vitro as well as in vivo during
infection with coxsackievirus B3. Genetic
dystrophin truncations lead to a marked decrease in
dystrophin-associated
glycoproteins, whereas expression of only the naturally occurring
dystrophin carboxyl terminus, Dp-71, restores the sarcolemmal 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 cardiac myocytes and murine hearts infected with coxsackievirus B3, the sarcolemmal localization of the
dystrophin carboxyl terminus is lost. The
dystrophin-associated
glycoproteins alpha-, beta-, gamma-, and
delta-sarcoglycan and
beta-dystroglycan were markedly decreased in the membrane fraction of infected cells in culture, and the typical sarcolemmal localization for each of these
proteins was lost in coxsackievirus-B3-infected cardiomyocytes in vivo. Furthermore,
sucrose gradient ultracentrifugation demonstrated that
delta-sarcoglycan was physically dissociated from
dystrophin within the membrane fraction. In vivo, the sarcolemmal integrity was functionally impaired with
Evans blue dye uptake even though there was no generalized disruption of the sarcolemma of infected myocytes evidenced by intact
wheat germ agglutinin staining. In analogy to hereditary
sarcoglycanopathies, this disintegration of the
sarcoglycan complex may, in addition to the
dystrophin cleavage, play an important role in the pathogenesis of enterovirus-induced
cardiomyopathy. These results imply a potential role for disruption of the
sarcoglycans in an acquired form of
heart failure.