Clinical and experimental aspects of viral myocarditis

Abstract

Picornaviruses are frequently implicated as the etiological agents of acute myocarditis. This association is based historically on serological evidence of rising antibody titers to specific pathogens and more recently on identification of viral genomic material in endocardial biopsy specimens through in situ hybridization. Only rarely is infectious virus isolated from either the patient or the heart during periods of maximum myocardial inflammation and injury. Thus, despite a probable viral etiology, much interest centers on the role of the immune system in cardiac damage and the likelihood that the infection triggers an autoimmune response to heart-specific antigens. Heart-reactive antibodies and T cells are found in most myocarditis patients, and immunosuppressive therapy has proven beneficial in many, though not all, cases. Furthermore, murine models of coxsackievirus group B type 3-induced myocarditis also demonstrate that virus infection initiates autoimmunity and that these autoimmune effectors are predominately responsible for tissue injury. How virus-host interactions overcome presumed self-tolerance to heart antigens is discussed, and evidence supporting various theories of virus-initiated autoimmunity and disease pathogenesis are delineated.

An aged host promotes the evolution of avirulent coxsackievirus into a virulent strain

“…versus day 3-7 p.i.) (13,23). Old CVB3͞0 Old -infected mice started becoming moribund by day 4 p.i., and, by day 8 p.i., 71% of the mice had died (Fig.…”

“…For the CVB3͞ 0 Adult passage control experiment, virus was isolated from infected adult mice during peak viremia (day 3 p.i.) (23), when adult mice have higher titers that can be isolated for passage.…”

“…Myocarditis due to CVB3 infections has been associated with the development of dilated cardiomyopathy, a common reason for heart transplants (23). Previous work by Beck et al (13,32,33) demonstrated that a normally amyocarditic CVB3, CVB3͞0, converts to a virulent and pathogenic species when passed through an antioxidant-deficient host (selenium, vitamin E, or glutathione peroxidase 1 knockout).…”

“…Coxsackieviruses, particularly strain B3 (CVB3), can cause an inflammation of the heart known as myocarditis and are believed to be the causative agent of Keshan's disease. CVB3 is primarily known for its etiologic role in Keshan's disease in children and young adults (23), but previous work has demonstrated that coxsackieviruses also are found in older adults and are likely grossly under diagnosed in this population (24,25). In addition, coxsackieviruses are known to cause pathology in humans in multiple other organs (24,(26)(27)(28)(29)(30)(31).…”

Inhibition of coxsackievirus B3 and related enteroviruses by antiviral short interfering RNA pools produced using φ6 RNA-dependent RNA polymerase

“…respiratory infections, myocarditis, meningoenchephalitides and generalized multiorgan infections of infants. CBV3 is the most common cause of viral myocarditis in humans (Bowles et al, 1986;Klingel et al, 1995;Leslie et al, 1989;McManus et al, 1991;Woodruff, 1980). The disease is often self-limiting and subclinical, but some acute infections are severe and lethal.…”