THE HERPES-SIMPLEX VIRUS TYPE-1 RIBONUCLEOTIDE REDUCTASE IS REQUIRED FOR ACUTE RETINAL DISEASE

We have used a herpes simplex virus type 1 (HSV-1) ribonucleotide redu ctase (RR) null mutant (ICP6 Delta) to determine if the HSV-1 RR is re quired for acute retinal disease. Injection of the ICP6 Delta mutant i nto the vitreous induced mild transient signs of infection (vitreal in filtrate, retinal inflammation, and changes in retinal cytology). In c ontrast, the parental KOS and a revertant virus (ICP6 Delta + 3.1) in which the RR gene had been restored, caused severe retinitis. Injectio n of media alone also induced mild transient signs of disease. Two mon ths after infection, ICP6 Delta injected eyes could not be distinguish ed from normal eyes. Repeated injection of ICP6 Delta (3 times, 2 week s apart) resulted in vitreal infiltrate near the site of injection but the retina did not appear damaged. The mutant, ICP6 Delta, grew to pe ak titers 1 x 10(3) to 1 x 10(5)-fold lower and cleared faster than KO S or ICP6 Delta + 3.1 in the injected eyes suggesting that the reduced virulence was due to reduced ability of the virus to grow. These resu lts show that the viral RR is required for acute retinal disease.