The pathological changes and distribution of virus antigen in mouse brains were studied following intracranial inoculation of 3 week old BALB/c mice with the herpes simplex virus (HSV) type 2 strain HG52 and its deletion variant JH2604. The variant JH2604 failed to produce necrotizing encephalitis compared to the parental HG52. The morphological changes induced in JH2604-infected brains consisted of localized perivascular cuffing by lymphocytes and infiltration by immune cells. Immunohistochemical studies using polyclonal anti-HSV serum showed that JH2604 antigens were localized at the site of inoculation with no evidence of neuronal involvement. Wild-type HSV-infected brains demonstrated a wide distribution of antigens both in neuronal and supporting cells. These data provide evidence that the non-neurovirulent phenotype of JH2604 is due to inability to replicate within neuronal cells of the central nervous system and pinpoints a precise role for the HG52 sequences contained within the 1488 bp subfragment of TR/IR deleted in JH2604.


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