Lethal encephalitis and non-lethal multifocal central nervous system demyelination in herpes simplex virus type 2 infections in mice.
Six-week-old Swiss-Webster mice were infected intracerebrally with a low dose of herpes simplex virus type 2 (HSV-2) and were studied by pathological, virological and immunological methods. One third of mice developed severe neurological disease and died during the first 31/2 weeks of infection, while the remaining two thirds survived this acute stage with relatively minor neurological signs. These survivors had multifocal demyelinative white-matter lesions in the CNS, and gray-matter lesions, if present, were few, small and usually minor. By contrast, groups of mice killed during the acute stage had a much greater proportion of gray-matter lesions, and these were frequently larger and more severe. Two subgroups could be identified in the acute stage. Mice with severe gray-matter disease, high virus titres, abundant viral antigen and later virus clearance had more severe neurological signs leading to death. By contrast, those destined to survive had pupillary signs alone, and pathologically had white-matter lesions of primary demyelination with minimal or no evidence of gray-matter involvement, low levels of detectable virus and earlier virus clearance. These results show that HSV-2 can produce non-lethal CNS disease in a high proportion of mice, even if infected by the intracerebral route, and that the lesions, which may be found throughout the CNS, are mainly in the white matter, and are demyelinative in type. Survivors of this infection may be useful in a search for evidence of herpes-virus persistence in the CNS, and for a role of this virus in chronic demyelinating disease.