The development of retinitis in mice with nonfatal herpes simplex encephalitis

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 weeks of inoculation. Histological examination revealed only a mild encephalitis, but around 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 only be recovered from the eye in the early stages of retinitis, destruction of the neural retina was frequently complete and subsequently the optic nerve showed Wallerian type degeneration. Visible cataracts were a late complication, but changes in the lens were initiated during the phase of acute retinitis. This experiment shows that 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 analogues, for example with acyclovir, could reveal the development of retinitis in survivors.