In North America and Europe, acute infectious myopericarditis and myocarditis are commonly caused by Coxsackie B virus, Types 1 through 5. The primary objective of this project is to identify the genetic control of host susceptibility to Coxsackie B3-induced heart muscle disease. We will examine the genetic influence of the major histocompatibility complex and other genes in the viral-induced and immunopathic myocarditis. We will test the hypotheses that the early lesions are a result of viral damage of the myocardial cells and the ensuing inflammatory response, and the later pathology is a result of an anti-myocardial autoimmune response. Genetic investigations will analyze recombinant inbred strains of mice and will also use segregation studies to identify the inheritance pattern (i.e. dominance, recessiveness, or codominance), location and number of genes controlling both the viral and autoimmune disease. All genetic segregation studies will be done by using serologically detectable alloantigens by hemagglutination or antibody-complement cytotoxicity and by using genetic markers distinguishable through their electrophoretic patterns. These markers will then be correlated with viral replication, viral neutralization, autoantibody production, early and late heart pathology and heart cellular infiltration. The genetic control of the humoral response, the class and specificity of antibody will be examined using viral neutralization, ELISA, and immunofluorescence assays. We will also examine the roles of the Class I and Class II genes play in both the viral and autoimmune diseases. This aim will be accomplished by examining H-2 congenic and intra-H-2 recombinant strains. Cell-mediated cytotoxicity will be used as an in vitro model to assess the role of cell-mediated immunity in both viral and autoimmune myocarditis. In vitro experiments will be done to examine strain differences in tissue trophism, viral replication, and interferon product. These investigations should aid in identifying the viral and immunological involved in susceptibility to myocarditis and to post CB3-induced cardiomyopathy.
|Effective start/end date||7/1/85 → 6/30/86|
- National Heart, Lung, and Blood Institute
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