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Immunohistochemical Studies on the Transneuronal Spread of Virulent Herpes Simplex Virus Type 2 and Its US3 Protein Kinase-Deficient Mutant after Ocular Inoculation
Authors:Mitsuaki Yamamoto  Ryutaro Kurachi  Tsuneo Morishima  Junzo Kito  Yukihiro Nishiyama
Abstract:The transneuronal spread of a virulent wild-type herpes simplex virus type 2 (HSV-2) and its US3 protein kinase-deficient (US3 PK?) mutant was immunohistochemically studied in mice after inoculations into the cornea, anterior chamber, tongue, and masseter muscle. After corneal inoculation, the wild-type virus was demonstrated in various brain stem areas including the trigeminal tract and nucleus, the reticular formation, and cerebellar nucleus group. Viral antigen-positive neurons were strictly confined to the ipsilateral spinal trigeminal nucleus in mice corneally infected with the US3 PK? mutant. No viral antigens were detected in the central nervous system (CNS) after inoculation with the mutant into the tongue and masseter muscle. However, when mice were immunosuppressed by treatment with cyclophosphamide, both the corneally infected mutant and wild-type virus could invade the CNS. The results suggest that the US3 PK? mutant principally retains the capacity to spread in the CNS.
Keywords:herpes simplex virus  neuroinvasiveness  protein kinase
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