• Beisel, Kirk, Emory University (PI)

Project: Research project

Project Details


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 date12/31/8912/31/89


  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute


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