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Molecular pathophysiological mechanisms in virus infected host myocardium

P. Liu1,1,2, P. Lee1,2, K. Fuse3 and M. Nian1,2

a Heart & Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario, Canada
b Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
c Niigata University, Niigata, Japan

1 Correspondence: Dr. Peter Liu (Heart & Stroke/Polo Chair Professor of Medicine at the University of Toronto), Heart & Stroke/RL Centre of Excellence, EN12-324, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada.

Abstract

The pathophysiological mechanisms of viral myocarditis are now better understood. The coxsackieviral receptors coxsackie adenoviral receptor (CAR) and decay accelerating factor (DAF) are linked to immune activation signalling pathways such as tyrosine kinase p56lck. Viral infection in murine knockout models has permitted identification of the mutually facilitatory roles of CD4 and CD8, which control the cytokine profile and the T-helper-1 versus T-helper-2 repertoire. The T-cell receptor associated tyrosine kinase p56lck is critical for disease progression, as in its absence the host will achieve 100% survival with limited viral replication. The major downstream target from p56lck is extracellular signal-related receptor , which is responsible for cytokine production in T cells and for viral proliferation in the host tissues. Finally, the system is modulated by the tyrosine phosphatase CD45. Recent investigations have provided an enriched environment from which to select future targets for intervention in the clinical arena, and have allowed expansion of these concepts to other types of heart failure.

References

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This Article
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