The herpes simplex virus ribonucleotide reductase is required for ocular virulence

We used a herpes simplex virus (HSV) type 1 ribonucleotide reductase (RR) null mutant (ICP6 delta) to study the role of HSV-1 RR in ocular HSV infections. We found that ICP6 delta was unable to induce vascularization of the cornea or stromal keratitis following inoculation into the cornea of BALB/c mice, but was able to induce a transient mild blepharitis. The parental strain (HSV-1 KOS) and a revertant of ICP6 delta, ICP6 delta+3.1, both caused severe ocular disease, indicating that HSV-1 RR is required for ocular virulence in mice. ICP6 delta grew poorly in vitro (Vero and BALB/c 3T3 fibroblasts) and in vivo (eye, trigeminal ganglia and brain) compared to ICP6 delta+3.1 and HSV-1 KOS, suggesting that the avirulence of ICP6 delta is due to poor growth in the host. ICP6 delta also grew less well in primary human corneal fibroblasts, suggesting that RR may be required for virulence in humans. These results indicate that drugs inhibiting the function of RR might be effective in treating ocular HSV infections.