Subacute infection with temperature-sensitive vesicular stomatitis virus mutant G41 in the central nervous system of mice. II. Immunofluorescent, morphologic, and immunologic studies.

Inoculation of three- to four-week-old BALB/c mice with temperature-sensitive (ts) vesicular stomatitis virus (VSV) mutant G41 produced a subacute neurological disease mainly localized in the spinal cord. Meningitis and diffuse microglial infiltration of the anterior horns of the spinal cord were seen starting six days after infection when neuronal degenerative changes could be seen. Infection of neurons was demonstrated by immunofluorescence microscopy five days after infection. Two to three weeks after infection, loosening of the neuropil was evident due to neuronal dropout, and the mononuclear infiltration had become perivascularly distributed and had changed in character because of a striking increase in plasma cells. These cells together with Russell bodies became the main inflammatory cellular component about four to five weeks after viral inoculation. Starting eight days after infection, several foci of primary demyelination could be found in the anterior columns of the spinal cord. Immunological responses appeared within four days after infection when both neutralizing antibody and stimulation of specific spleen lymphocytes could be demonstrated. Serum antibody responses peaked at 21-28 days but remained elevated for up to 153 days. Stimulation of spleen lymphocyte cells peaked at 10-21 days and also remained elevated for as long as 116 days. The presence of both inflammatory changes and immunological responses to VSV mutant ts-G41 for prolonged periods is characteristic of persistent viral infections. Infection of BALB/c mice with ts-G41 thus represents the first in vivo example of persistent viral infection utilizing ts mutants of VSV.