Estrogen receptor signaling protects female mice from lethal MA15 infection. Nine- to ten-month-old male and female and their gonadectomized counterparts were infected with 5000 PFU MA15. Nine-month old gonadectomized (n = 8) or nongonadectomized (n = 8) (A) and control (n = 6) or flutamide-treated (n = 7) (B) male mice were monitored for disease severity. (C) Percentage of initial weight and survival among control (n = 12) or ovariectomized female (n = 12) mice. (D) Female mice treated with vehicle (corn oil; n = 9), tamoxifen (1 mg per mouse; n = 9–10), or ICI 182, 780 (1 mg per mouse; n = 10) in 100 μl of corn oil were infected with 5000 PFU MA15 and monitored for morbidity and mortality. Data are derived from two or three independent experiments with three to five mice per group per experiment. *p < 0.05, **p < 0.01, log-rank test with 95% CI.