Inoculation of dengue virus into nude mice.

When athymic nude (nu/nu) and heterozygous littermate (nu/+) mice were injected intraperitoneally (i.p.) with a mouse-adapted strain of dengue virus (DV), the following differences were noted in the course of infection. (i) The average survival time of nu/nu mice was longer than that of nu/+ mice, although the mortality ratios were not significantly different. (ii) DV persisted in some of the nu/nu mice for long periods of time without exhibiting any symptoms but they died after prolonged incubation periods. These aspects were not observed in the nu/+ mice. (iii) Infected nu/nu mice produced IgM antibody only transiently in the early stage of infection but they did not subsequently show regular IgG antibody production which normally occurred in nu/+ mice. (iv) Piamatral and perivascular mononuclear cell infiltration in the infected brain was more intense in nu/+ than in nu/nu mice. It is suggested from these data that the course of DV infection in mice is affected by the availability of thymus-derived lymphocytes (T-cells). Infectious virus was detected in various organs and tissues of infected mice. The hearts of nu/nu mice tended to show higher virus titres than those of nu/+ mice, whereas the virus concentrations in the brain, skeletal muscle and lymph node were the same in both groups of mice. Specific DV antigen was revealed by the fluorescent antibody (FA) technique in cells located in the infected tissues.