Enteroviruses such as Coxsackievirus B3 can cause dilated cardiomyopathy, but the mechanism of this pathology is unknown. Mutations in cytoskeletal proteins such as dystrophin cause hereditary dilated cardiomyopathy, but it is unclear if similar mechanisms underlie acquired forms of heart failure. We demonstrate here that purified Coxsackievirus protease 2A cleaves dystrophin 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 the dystrophin-associated glycoproteins alpha-sarcoglycan and beta-dystroglycan are morphologically disrupted in infected myocytes. We suggest a molecular mechanism through which enteroviral infection contributes to the pathogenesis of acquired forms of dilated cardiomyopathy.

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.

Genetic deficiency of the dystrophin-glycoprotein complex causes hereditary dilated cardiomyopathy. Enteroviruses can also cause cardiomyopathy and we have recently described a potential molecular mechanism for enterovirus-induced dilated cardiomyopathy. The coxsackieviral protease 2A proteolytically cleaves and functionally impairs dystrophin. Additionally, during infection with coxsackievirus B3, the dystrophin-glycoprotein complex becomes disrupted and the sarcolemmal integrity is lost. This review article discusses the importance of the dystrophin cleavage for the development of increased sarcolemmal permeability and potential pathways for mechanisms by which the dystrophin cleavage during coxsackieviral infection may contribute to dilated cardiomyopathy.

Growth curves for ultrasonic carcass traits such as longissimus muscle area, backfat thickness and marbling score as well as chest girth which was simultaneously measured when carcass traits were investigated using ultrasound measuring technique were estimated to identify growth patterns and to adjust maturing effects in order to evaluating genetic merits on cows in farming basis. 27,410 records from 22,451 cows on which of 15~90 month of age were investigated from the national wide of Korea using by ultrasonic scanning techniques by the skilled persons from 2002 to 2007. Van Bertalanffy growth function was applied for estimating growth curves on these traits. Carcass traits and chest girth would be linearly increased by body condition score. It might be used for multiplicative correction factors for preadjustment on the body condition scores. Growth pattern on chest girth would be quickly reached to mature size and stable on after reached to asymptotic mature size. Longissimus muscle area would also be reached to mature size but little smoother than chest girth. Otherwise, growth curve on backfat thickness would be steadily increasing up to 7 years of age. It also showed large individual difference by way of mean square error. Marbling score would be steadily increased but sharper than those on backfat thickness. It would be reached to mature size up at 5 years of age. Those growth curves would be used for correcting function on age at investigating on genetic evaluation system.

No abstract