Characterisation of murine cytomegalovirus myocarditis: cellular infiltration of the heart and virus persistence.

Myocarditis triggered by a viral infection has integral viral and immunological aspects associated with the pathogenesis of disease. The present study was performed to analyse the cellular inflammatory response in the heart and cytomegalovirus replication during the development of myocarditis in vivo. We examined murine cytomegalovirus in an animal model of myocarditis using both susceptible BALB/c and resistant C57BL/6 mice. The heart infiltrating cells of BALB/c mice were found to comprise predominantly CD8+ T cells, with other cells of the CD4+ T cell, macrophage, B cell and neutrophil phenotype. Infectious MCMV titres in the heart were low and replicative virus could not be isolated beyond the first week post-infection (p.i.). Direct viral lysis of myocytes in vitro and apoptosis of cardiac cells in vivo was observed. Furthermore, viral DNA was detected in the heart of both mouse strains throughout the development of chronic disease. Viral gB RNA was detected during the first 35 days p.i. However, viral transcript for ie1 RNA but not gB RNA was found in the heart during the late stage of disease, suggesting latent viral infection of the heart. Our findings suggest that maintenance of the chronic phase of myocarditis involving post-viral immunological responses can occur in the presence of little infectious virus replication in the heart. Copyright 2002 Elsevier Science Ltd. All rights reserved.