The pathogenesis of Sindbis virus infection in athymic nude mice

The pathogenesis of avirulent Sindbis virus infection was studied in normal and athymic nude mice. Marked differences in the immune response to infection were observed in nude and normal animals. In contrast to the intense mononuclear inflammatory cell response seen in the brains of normal mice 5 to 7 days after intracerebral injection of Sindbis virus, minimal inflammatory changes were observed in nude mouse brains. In addition, only IgM anti-Sindbis virus antibody was detected in nude mice whereas normal animals produced IgG as well. Despite these differences, the clinical outcome of the infection and the clearance of virus from the CNS was the same in both groups of mice. After footpad inoculation of virus, the lymphoproliferative response of popliteal lymph node cells (LNC) from nude mice to Sindbis virus were meager or absent whereas normal LNC responded well (stimulation index = 38, 6 days after infection). Differences in the kinetics of the neutralizing antibody response to Sindbis virus were also observed. Although Ab production was not different through day 6, normal animals possessed 10-fold more anti-viral antibody 10 days after inoculation. It is concluded from these studies that mature T cells do not play a role in the clearance of Sindbis virus from the CNS of mice and that the early Ab response (IgM) and/or nonspecific defense mechanisms may be of greater importance in recovery from acute viral encephalitis.