title: Molecular analysis of clinical isolates of acyclovir resistant herpes simplex virus.
abstract: We characterised the antiviral phenotype and genotype of 41 herpes simplex virus (HSV) strains from patients clinically resistant to acyclovir (ACV). Our results confirm recognised mutational sites as being major determinants of thymidine kinase (tk)-associated ACV resistance, in particular insertions and/or deletions at homopolymer stretches of Gs and Cs (59% of all isolates). Previously described amino acid substitutions in functional sites of the tk were also identified (7% of all isolates). In addition, we identified several stop codons in novel locations on the amino acid sequence (7% of all isolates) and amino acid substitutions (15% of all isolates) likely to be directly responsible for conferring resistance to ACV. When there were no mutations detected in the tk gene (12% of all isolates), mutations in the DNA polymerase gene likely to be important in the generation of resistant virus were identified.
authors.affiliation: Victorian Infectious Diseases Reference Laboratory, 10 Wreckyn Street, Victoria 3051, North Melbourne, Australia. Doris.chibo@mh.org.au
authors.forename: Doris
authors.initials: D
authors.lastname: Chibo
authors.forename: Julian
authors.initials: J
authors.lastname: Druce
authors.forename: Joe
authors.initials: J
authors.lastname: Sasadeusz
authors.forename: Chris
authors.initials: C
authors.lastname: Birch
mesh_terms: D000212:Acyclovir / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006561:Herpes Simplex / Q000188:drug therapy* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D013937:Thymidine Kinase / Q000235:genetics
chemical_list: D004279:DNA, Viral; D013937:Thymidine Kinase; D000212:Acyclovir