Characterization of encephalitis in adult mice induced by intracerebral inoculation of herpes simplex virus type 1 (KOS) and comparison with mutants showing decreased virulence.
The spread of herpes simplex virus type 1 (HSV-1) strain KOS, and two less neurovirulent mutants of the strain was studied in female DBA/2 mice during the 1- to 5-day postinoculation period after intracerebral inoculation. Immunohistopathology showed that wild-type KOS virus first infected the meninges and ependymal cells but did not infect cells at the inoculation sites. The virus continued to spread to some cells directly adjacent to ventricles; however, the most extensive and severe lesions were found in the pyriform lobes and other structures associated with the limbic system. The pattern of spread suggested that direct cell to cell viral spread is important but that retrograde axonal transport to distant sites probably accounts for the more severe lesions associated with the limbic system. Both less neurovirulent mutant viruses multiplied to a much lesser degree in the brain and spread less extensively than the wild type virus when equivalent doses were given; however, when a large dose of the least neurovirulent mar C10.1 mutant virus was inoculated, infection spread rapidly to the same regions of the brain affected by KOS. Studies of mar C10.1 showed that thymidine kinase deficiency, rather than a mutation in the gene coding for glycoprotein C, probably accounted for the decreased neurovirulence of this mutant. This mouse model of HSV-1 virus-induced encephalitis, in combination with appropriate studies of the molecular biology of the HSV-1 KOS strain, should be useful for the study of neurovirulence factors contributing to the pathogenesis of HSV-1.
Chrisp
C E
CE
Department of Human Genetics, University of Michigan Medical School, Ann Arbor.
Sunstrum
J C
JC
Averill
D R
DR
Levine
M
M
Glorioso
J C
JC
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001921:Brain / Q000382:microbiology / Q000473:pathology; D004660:Encephalitis / Q000382:microbiology* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006561:Herpes Simplex / Q000382:microbiology* / Q000473:pathology; D007124:Immunoenzyme Techniques; D051379:Mice; D008811:Mice, Inbred DBA; D009154:Mutation; D009336:Necrosis; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D014774:Virulence; D014779:Virus Replication
D000956:Antigens, Viral