136 Characterization of acyclovir-resistant herpes simplex virus collected by the task force on herpesvirus resistance : M. G. Davis, A. Root, C. L. Talarico, W. K. Lawrence, and the Task Force on Herpesvirus Resistance, Glaxo Wellcome, Inc. Research Triangle Park, NC, USA

Abstract

Twenty-four strains of acyclovir (ACV)-resistant (ACVr) herpes simplex virus type 1 (HSV-1) were generated from the HSV-1 TAS strain by exposure to ACV, and the genotype and phenotype of the thymidine kinase (TK) from these mutants were analyzed. The TK polypeptide of the ACVr HSV-1 strains was examined by Western blot using an anti-HSV-1 TK rabbit serum. The sensitivity of each strain to ACV, foscarnet and cidofovir (CDV) was also determined. A single guanine (G) insertion or a single cytosine (C) deletion was detected in 12 of the 24 ACVr strains at the G or C homopolymer stretches within the TK gene. Genotypic analysis predicted that two thirds of the ACVr HSV-1 strains expressed truncated TK polypeptides, while one third expressed viral TK polypeptide with a single amino acid substitution at various sites. Western blot abnormalities in the viral TK polypeptides were identified in 21 ACVr strains. There was an inverse correlation between the susceptibility of the HSV-1 mutant strains to ACV and that to CDV. Nucleotide sequencing of the TK gene and Western blot analysis of the viral TK polypeptides are considered to be one of the methods for predicting virus sensitivity to ACV and CDV.