CARDIAC MUSCLE DISEASE AND ENTEROVIRUS PRESENCE

The long-term goal of the proposed research is to correlate
enteroviral presence in the heart, and perhaps other organs, with
causation of acute myocarditis which progresses to chronic
myocardial diseases such as dilated cardiomyopathies. The two
specific aims of the work are (1) to examine the role of the
inducing coxsackievirus B3 and murine genetic backgrounds
through in situ hybridization detection of viral RNA in many
murine tissues during disease progression following viral
innoculation; (2) to sensitively probe human heart tissue and
peripheral blood mononuclear cells of clinically well-
characterized myocarditis patients and myocardium of explanted
dilated hearts for the presence of enteroviral genomes and to
develop a rapid, sensitive assay for enteroviral RNA using
enzymatic amplication of nucleotide sequences and novel
enhanced rate hybridization kinetics capable of detecting in the
range of 10-100 enteroviral RNa molecules in biopsy within hours.
The mouse model will be employed to determine what effects the
virulence of the virus and the host genetic background have on
viral persistence, disease progression, and presence of virus in the
chronic phase of the disease and to draw inferences to the
presumed homologous human situation. These experiments will
provide essential data to evaluate whether enteroviruses remain
in tissues other than heart following acute infection, perhaps
acting as seeds to promote the inflammatory processes which
have been demonstrated as deleterious to the heart in chronic
disease. Screening of human hearts for enteroviral RNA, by in
situ hybridization and later using a more sensitive approach
developed in the course of this work, will determine whether
enteroviral presence and presence of pathologic changes in the
affected human organ can be correlated. Cumulatively, these
experiments will determine whether there is justification to
pursue prophylactic measures against specific enteroviruses as
causes of human myocarditis and cardiomyopathies.