Cardiomyocyte apoptosis in experimental coxsackievirus B3 myocarditis.
BACKGROUND
Viruses are known to induce apoptosis in their host cells. We studied whether cardiomyocyte apoptosis occurs upon coxsackievirus B3 (CVB3) infection and whether virus-associated apoptosis plays a role in the pathogenesis of experimental myocarditis.


METHODS
BALB/c mice were infected with two variants of CVB3 causing either mild or severe myocarditis. Myocardial and serum samples were collected from Day 1 to Day 14 after virus inoculation. Apoptosis was detected in myocardial tissue sections using the terminal transferase-mediated DNA nick end labelling (TUNEL) assay and staining of active caspase 3, and compared with the presence of infectious CVB3 and viral proteins in cardiomyocytes.


RESULTS
Compared with the noninfected control mice, infection with either CVB3 variant resulted in significantly increased cardiomyocyte apoptosis, which peaked on Day 5 after infection. At this time, the average percentages of apoptotic cardiomyocytes were 0.17% (SD 0.04; P=.03) and 0.77% (SD 0.11; P<.01) in mild and severe disease forms, respectively. The amount of apoptosis correlated with titers of infectious CVB3 in the heart muscle. Viral proteins were detected in the TUNEL-positive cells by immunohistochemistry. In the late stages of disease, apoptosis, together with inflammatory infiltrates persisted only in the severe disease form.


CONCLUSIONS
CVB3-associated myocardial damage involves cardiomyocyte apoptosis. In the early stages of the disease, it appears to be triggered by viral replication in the cardiomyocytes.
D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000150:complications / Q000473:pathology*; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000473:pathology* / Q000821:virology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000032:analysis
D012367:RNA, Viral; D014764:Viral Proteins