The pathogenic concepts of viral myocarditis (MC) and associated cardiomyopathies (DCMi) has continuously evolved during the past decades. The failure of conventional virological ( e.g. virus isolation) and histopathological methods to detect a cardiac viral infection led to the concept of autoimmune MC as a postviral immune-mediated disease. The advent of molecular biological methods led to the rediscovery of the virus etiology of MC. It also became clear that virus-associated inflammation of the myocardial vessels (vasculitis) may be involved into pathogenesis of DCMi. The concept of viral etiologies of DCMi has been developed on the basis of in situ hybridization and polymerase chain reaction (PCR) techniques. By these means several viruses were newly identified as cardiotropic agents in the human heart, too. In addition to the "classical" enteroviruses (EV) adenoviruses (ADV), herpesviruses (HHV6, EBV, HSV, HCMV) and parvovirus B19 (PVB 19) were detected in association with DCMs. The enormous clinical and health economical impact of DCMi incited intensive research on the cardiopathogenic relevance of these viral agents, and on host- and virus-specific pathogenicity determinants. The five projects of SFB area B focus on the analysis of molecular pathomechanisms in virus-induced cardiac inflammation and their therapeutic modulation. From a molecular biological viewpoint virus-associated inflammatory reactions are attractive models to study virus-cell-interactions, e.g. by investigating virus- and host-encoded genes and gene clusters including those associated with immune reactions. This work requires an interdisciplinary approach involving molecular and cell biology, immunology, genetics, clinical cardiology, and population-based- epidemiology which is implemented in the SFB/TR 19. Mechanisms of both innate and acquired immunity are involved in the pathogenesis of DCMi, e.g. the humoral response (B-cells, antibodies)and the cellular defense including T-cells with their known subgroups. The antiviral immune response should efficiently eliminate the virus while not damaging the host. Inflammation is primarily a physiological process aimed at tissue repair. Chronic inflammation, however, results in tissue destruction, whereas lack of inflammation leads to virus persistence. The regulatory mechanisms underlying appropriate immune and inflammatory responses are exceedingly complex and subject of the projects B1 to B5. |
