PHENOTYPIC AND GENOTYPIC CHARACTERIZATION OF ACYCLOVIR-RESISTANT HERPES-SIMPLEX VIRUSES FROM IMMUNOCOMPROMISED PATIENTS

Phenotypic and genotypic analyses were done on 30 acyclovir-resistant and 5 acyclovir-susceptible herpes simplex virus (HSV) isolates (22 HS V type 1 and 13 HSV type 2) recovered from 24 subjects, All isolates w ere susceptible to foscarnet, The phenotypes of the acyclovir-resistan t HSV isolates were as follows: 17 were thymidine kinase (TK) deficien t, 12 had decreased TK activity (produced low amounts of viral TK) or TK with altered substrate specificity, and 1 was undetermined, Sequenc ing analysis of the HSV TK gene revealed that 14 (46.7%) of 30 acyclov ir-resistant isolates had an insertion or deletion of 1 or 2 nucleotid es, especially in homopolymer runs of Gs, Cs, and rarely in As. On the other hand, 16 (53.3%) of 30 acyclovir-resistant isolates had point m utations in conserved or nonconserved regions of the TK gene, In concl usion, HSV can develop multiple strategies to exhibit acyclovir resist ance, including, in about half of the cases, frameshift mutations in h omopolymer nucleotide stretches of the TK gene.