It is still unclear why so many human LACV infections remain asymptomatic. In our mouse model, infection with 1 LD 50 of virus resulted in delayed CNS infection compared to mice receiving 100 LD 50 . Mice were able to control virus infection at doses at or below the LD 50, and developed strong neutralizing antibody responses. The LACV ID 50 for humans is unknown, but if human exposure is limited to a small dose, the virus may be effectively controlled by the immune system and CNS infection may be averted. If, like our mouse model, an individual is exposed to a greater dose of virus, virus growth may outpace control mechanisms leading to CNS infection. To further support the role of immune control affecting human disease outcome, it has been shown that individuals residing in endemic areas with major histocompatibility complex molecule B49 on CD8+ cytotoxic T lymphocytes (HLA-B49) had a greater relative risk of developing encephalitis after infection (relative risk 17.65, χ 2 = 7.3, P < 0.1). Infected individuals with HLA-DR5 had a lower relative risk of developing seizures (relative risk 0.22, χ 2 = 5.10, P < 0.025) [41] .