Acyclovir-resistant mutants of herpes simplex virus type 1 express altered DNA polymerase or reduced acyclovir...

The biochemical properties of four acyclovir-resistant mutants are described. Two of these mutants, PAAr5 and BWr, specified nucleotidyl transferase (DNA polymerase) activities which were less sensitive to inhibition by acyclovir triphosphate than their wild-type counterparts. Another mutant, IUdRr, exhibited reduced ability to phosphorylate acyclovir. The fourth mutant, ACGr4, both induced an altered DNA polymerase and failed to phosphorylate appreciable amounts of acyclovir. BWr, a new acyclovir-resistant mutant derived from the Patton strain of herpes simplex virus type 1, induced a DNA polymerase resistant to inhibition by acyclovir triphosphate, but, unlike the polymerases induced by PAAr5 and ACGr4, still sensitive to phosphonoacetic acid. Resistance of BWr to acyclovir mapped close to the PAAr locus and was separable from mutations in the herpes simplex virus thymidine kinase gene by recombination analysis.