Myocarditis susceptibility in female mice depends upon ovarian cycle phase at infection

Female BALB/c mice were infected with coxsackievirus B3 in the diestrus, proestrus, estrus, or metestrus phases of the ovarian cycle. Cycle stage was determined by vaginal smear. All mice were killed 7 days after infection. Females infected in the diestrus and especially the proestrus phases developed myocarditis. CD4+ T cells expressing interferon-gamma (IFNgamma) infiltrate the myocardium in these two phases, whereas CD4+ T cells expressing IL-4 are more frequent during estrus. Cardiac virus titers were determined 15 h and 7 days after infection. No differences in virus titer were seen at 7 days. These studies show that natural hormone variations can have substantial effects on viral pathogenicity presumably due to hormone effects on the immune system.