Ribonucleotide Reductase Encoded by Herpes Simplex Virus Is a Determinant of the Pathogenicity of the Virus in Mice and a Valid Antiviral Target

1 Glaxo Group Research Limited, Greenford Road, Greenford, Middlesex UB6 0HE and 2 MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, U.K. The role of the herpes simplex virus (HSV)-encoded ribonucleotide reductase (RR) in the pathogenicity of the virus has been examined by use of mutants with lesions in either the large or small subunit of the enzyme. The virulence of the mutants in mice was reduced by about 10 6 -fold when compared with that of the parental virus (HSV type 1 strain 17), while the virulence of a revertant of one of the mutants was restored to within about 100-fold of that of the parent virus. These experiments demonstrate that activity of the HSV RR is essential for virus pathogenicity in mice and suggests that the enzyme is a valid target for specific antiviral compounds. Keywords: HSV, ribonucleotide reductase, pathogenicity Received 3 March 1988; accepted 13 July 1988.