Differential Susceptibility and Resistance of Immunocompetent and Immunodeficient Mice to Fatal Hantaan Virus Infection

Susceptibility and resistance to fatal Hantaan virus meningoencephalitis were studied in immunocompetent (nu/+) and congenitally T-cell deficient (nu/nu) CD-1 mice of different ages. Susceptibility of nu/+ mice to fatal infection was age-dependent, as evidenced by 100 percent mortality in mice inoculated intracerebrally with Hantaan virus (strain 76-118) during the first week of life, 60 percent mortality in mice inoculated at 9 days of age, and no disease or death in mice inoculated at 14 to 42 days of age. Deaths occurred significantly earlier in nu/+ mice inoculated at 5 and 7 days of age than in nu/+ mice less than 24 hours old. Nu/nu littermates of the same age did not exhibit a similar inverse relationship between age and survival times. Moreover, nu/nu mice 14 days or older remained susceptible, albeit with delayed onset of illness and time of death. Virus titers in brain tissues of nu/+ mice inoculated at 7 days and of nu/nu mice inoculated at 7, 9 and 14 days of age were nearly identical. In older nu/+ mice, peak virus titers were comparatively lower, but they did not seem to be influenced by the magnitude of the neutralizing antibody response. The more rapidly fatal course in nu/+ mice inoculated at a week of age than at birth, and the differential resistance between weanling nu/+ and nu/nu mice to Hantaan virus meningoencephalitis suggest that cell-mediated immunity may be responsible for both enhancement of disease and recovery from infection.