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1 Department of Ophthalmology
and2 Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin 53706, U.S.A.
We used a herpes simplex virus (HSV) type 1 ribonucleotide reductase (RR) null mutant (ICP6
) to study the role of HSV-1 RR in ocular HSV infections. We found that ICP6 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, ICP6+ 3.1, both caused severe ocular disease, indicating that HSV-1 RR is required for ocular virulence in mice. ICP6 grew poorly in vitro (Vero and BALB/c 3T3 fibroblasts) and in vivo (eye, trigeminal ganglia and brain) compared to ICP6+3.1 and HSV-1 KOS, suggesting that the avirulence of ICP6 is due to poor growth in the host. ICP6 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.
Received 30 November 1990;
accepted 15 May 1991.
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