Links Between Viral Infections and Heart Disease

Coxsackievirus experimental heart diseases

“…CVB3 infections of mice and humans induce autoimmune reactions in both humoral and cell-mediated immune systems (15,17,32). Epitopes shared by surface regions of the three capsid polypeptides and normal cell proteins have been readily demonstrated by showing that during a CVB3 infection of mice, autoantibodies were detected against several cell antigens by cytolytic complement-fixation assays, ELISA titrations, by immunoblot reactions and/or by immunocytochemistry (15,18,37). In infected mice, a list of the normal murine cell proteins that share epitopes with CVB3 capsid proteins, as recognized by autoantibodies or autoreactive lymphocytes, is presented in Table 2 (15,17,32).…”

“…Those murine strains in which virus infection induces gamma/delta T cells will subsequently promote a Th 1 inflammatory cell response against infected cells in heart tissues, a type of immune response crucial to development of chronic disease (35,56,73). Another major parameter that likely contributes to maintenance of chronic inflammation in the heart of select murine strains is the persistent synthesis of viral RNA in absence of infectious virus (37). Viral RNA synthesis has been detected in heart tissues of mice and humans with myocarditis by in situ hybridization (78) and by RT-PCR (79).…”

“…Viral RNA synthesis has been detected in heart tissues of mice and humans with myocarditis by in situ hybridization (78) and by RT-PCR (79). Only murine strains that develop chronic myocarditis in response to inoculation by a cardiovirulent CVB3 develop persistent viral RNA synthesis in heart tissues, whereas murine strains that resolve the disease do not permit this continued synthesis of viral RNA (37,80). A well-studied noncardiovirulent CVB3 strain (CVB3 0 ) did not persist in heart tissues via RNA synthesis in a murine strain capable of developing chronic myocarditis (37).…”

“…Only murine strains that develop chronic myocarditis in response to inoculation by a cardiovirulent CVB3 develop persistent viral RNA synthesis in heart tissues, whereas murine strains that resolve the disease do not permit this continued synthesis of viral RNA (37,80). A well-studied noncardiovirulent CVB3 strain (CVB3 0 ) did not persist in heart tissues via RNA synthesis in a murine strain capable of developing chronic myocarditis (37). In studies of persistence of viral RNA synthesis in a transformed mouse cardiac fibroblast cell line, data were generated which suggested that virus-induction of IFN-beta likely played a contributing role in maintenance of viral RNA synthesis at a low level in these cells (37).…”

“…A well-studied noncardiovirulent CVB3 strain (CVB3 0 ) did not persist in heart tissues via RNA synthesis in a murine strain capable of developing chronic myocarditis (37). In studies of persistence of viral RNA synthesis in a transformed mouse cardiac fibroblast cell line, data were generated which suggested that virus-induction of IFN-beta likely played a contributing role in maintenance of viral RNA synthesis at a low level in these cells (37). It was hypothesized that the continued presence of viral RNA, likely at sites of focal inflammation in mouse heart tissues (78), induced production of proinflammatory cytokines that participated in maintaining the inflamed state in the heart (37).…”