Atypical Patterns of Neural Infection Produced in Mice by Drugresistant Strains of Herpes Simplex Virus

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Abstract
Mice inoculated intracerebrally (i.c.) with a mutant strain of herpes simplex virus developed cataracts 1-2 mo. after inoculation. Cataract formation was subsequently shown to follow an acute retinitis which commenced within 1 wk of inoculation. The mutant was selected for high resistance to the nucleoside analog acyclovir and was shown to be defective in the induction of thymidine kinase and to express an altered DNA polymerase. The LD50 for mice inoculated i.c. was > 10 plaque-forming units (p.f.u.) compared with .apprx. 7 p.f.u. for the parental strain. Studies of virus replication following i.c. inoculation with a sublethal dose of the mutant revealed that only small amounts of infectious virus were produced in the brain, but during a period 6-12 days after inoculation, vigorous replication occurred in retinal tissue, producing very high virus titers.