The sensitivity of acyclovir-resistant mutants of herpes simplex virus to other antiviral drugs.

Three acyclovir (ACV)-resistant mutants derived from a strain of herpes simplex virus (HSV) type 1 were studied to determine the range of their resistance to nine drugs active against HSV. Two of the mutants were thymidine kinase-deficient (TK-) and were resistant to drugs that are usually phosphorylated by HSV TK. The other mutant induced normal levels of TK; it was of special interest since TK+ viruses appear more likely to multiply well in vivo. This mutant was inhibited by "TK-mediated" drugs: idoxuridine, which is already in use, and two drugs with promising clinical potential, 1-beta-arabinofuranosylthymine and E-5-(2-bromovinyl)-2'-deoxyuridine. All of the mutants were sensitive to trifluorothymidine and 9-beta-D-arabinofuranosyladenine. These results suggest that the study of cross-resistance of HSV strains in vitro will aid in the investigation of alternative drugs for use in effective chemotherapy.