Extending Human Induced Pluripotent Stem Cell Technology to Infectious Diseases
New Model for Viral Myocarditis
Infections by viruses, such as adenoviruses, enteroviruses, or parvoviruses, can affect the heart, resulting in myocardial inflammation.1 Viral myocarditis encompasses a wide spectrum of clinical presentations, ranging from oligosymptomatic infections to the rapid development of terminal heart failure.
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Clinical diagnosis of viral myocarditis remains a challenge. Although modern imaging modalities, such as late gadolinium enhancement MRI, can be used to estimate the likelihood of viral heart disease in suspected cases, the definite diagnosis still requires histopathologic examination of endomyocardial biopsies.2 Viral heart disease seems to account for a relevant proportion of otherwise unexplained dilated cardiomyopathies. In large series of patients with this diagnosis who underwent endomyocardial biopsy, myocarditis was found in ≈10% of cases.3,4 Because of the unavailability of specific noninvasive tests, the exact prevalence of viral myocarditis is unknown, and it is likely that many cases remain undiagnosed.5
One of the most prevalent and most intensively studied myocarditis-causing viruses is coxsackievirus B3, a member of the enterovirus genus of unenveloped single-stranded positive-sense RNA viruses. The entry of coxsackieviruses into cardiomyocytes depends on surface expression of the coxsackievirus and adenovirus receptor, a transmembrane protein with 2 extracellular immunoglobulin domains that is highly expressed on the cell membrane of cardiomyocytes.6
Upon replication in the host myocardium, a protein called enteroviral protease 2A is synthesized, which was demonstrated to cleave the sarcolemmal protein dystrophin specifically, disrupting the cytoskeletal integrity of the cardiomyocytes.7
Much of our knowledge of the …