Cardiac cell-specific apoptotic and cytokine responses to reovirus infection: determinants of myocarditic phenotype.
BACKGROUND
The pathophysiologic mechanisms underlying viral myocarditis are not well defined. As a result, effective treatments do not exist and viral myocarditis remains a potentially lethal infection of the heart.


RESULTS
We used cultured rat cardiac myocytes and fibroblasts to investigate apoptosis and cytokine production in response to infection by myocarditic vs. non-myocarditic strains of reovirus. Myocarditic reovirus strain 8B and non-myocarditic strain DB188 replicate comparably in each cardiac cell type. However, strain 8B and related myocarditic reoviruses preferentially increase apoptosis of myocytes relative to fibroblasts, whereas DB188 and nonmyocarditic strains preferentially increase fibroblast apoptosis. Infection of cardiac fibroblasts with the nonmyocarditic strain DB188 elicits substantial increases in a panel of cytokines compared to fibroblasts infected with strain 8B or mock-infected controls. Analysis of culture supernatants using cytometric bead arrays revealed that DB188 enhanced release of interleukin (IL)-1beta, IL-4, IL-6, IL-10, IL-12(p70), GRO-KC, tumor necrosis factor-alpha, and MCP-1 relative to 8B or mock-infected controls (all P < .05).


CONCLUSIONS
We hypothesize that differential cytokine production and cell-specific apoptosis are important determinants of myocarditic potential of reoviral strains. Therapies that target the beneficial effects of cytokines in limiting cytopathic damage may offer an effective and novel treatment approach to viral myocarditis.
Miyamoto
Shelley D
SD
Department of Pediatrics, University of Colorado Denver Health Sciences Center, Denver, Colorado, USA. Miyamoto.shelley@tchden.org
Brown
R D
RD
Robinson
Bridget A
BA
Tyler
Kenneth L
KL
Long
Carlin S
CS
Debiasi
Roberta L
RL
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D009205:Myocarditis / Q000473:pathology* / Q000821:virology; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000821:virology; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D012088:Reoviridae Infections / Q000473:pathology*
D016207:Cytokines