THE DEVELOPMENT OF RETINITIS IN MICE WITH NONFATAL HERPES SIMPLEX ENCEPHALITIS

Abstract

A mutant strain of herpes simplex virus type 1 (HSV1) selected for high resistance to acyclovir (ACV) was inoculated intracerebrally into mice. The mice survived with no obvious neurological signs but developed cataracts within 4-8 wk of inoculation. Histological examination revealed only a mild encephalitis, but .apprx. 7 days after injection a florid, necrotizing, viral retinitis developed. There was almost simultaneous involvement of both eyes. Inflammatory cell infiltration and early myelin degeneration along the course of the optic nerve suggested cell to cell spread of virus to the retinal nerve cell bodies. Although virus could be recovered from the eye only in the early stages of retinitis, destruction of the neural retina was frequently complete and subsequently the optic nerves showed Wallerian type degeneration. Visible cataracts were a late complication but changes in the lens were initiated during the phase of acute retinitis. Thus, antiviral agents may induce mutant forms which cannot reproduce classical disease, but are capable of permissive infection in unexpected sites. Herpes retinitis is occasionally recognized as a complication of fatal HSV encephalitis in man. Theoretically, more effective treatment of encephalitis with nucleoside analogs, e.g., acyclovir, could reveal the development of retinitis in survivors.