G. Boivin et al., PHENOTYPIC AND GENOTYPIC CHARACTERIZATION OF ACYCLOVIR-RESISTANT VARICELLA-ZOSTER VIRUSES ISOLATED FROM PERSONS WITH AIDS, The Journal of infectious diseases, 170(1), 1994, pp. 68-75
Phenotypic and genotypic analyses were done on 17 varicella-zoster vir
us (VZV) isolates recovered from 10 persons with AIDS (mean CD4 cell c
ount, 16.4/mm(3)) who had chronic VZV lesions. Eleven acyclovir-resist
ant isolates were recovered from 10 patients after a mean of 20.1 week
s of therapy. Six susceptible isolates were recovered before acyclovir
treatment (n = 1), early during therapy (n = 4; mean time, 4.2 weeks)
, or after discontinuation of acyclovir (n = 1). Acyclovir-resistant V
ZV isolates were deficient in thymidine kinase (TK) or induced a TK wi
th altered substrate specificity; all isolates were susceptible to fos
carnet. Ten of 11 acyclovir-resistant mutants contained tk gene mutati
ons, including single nucleotide substitutions in highly conserved bin
ding sites (n = 2) as well as nucleotide deletions (n = 4) and inserti
ons (n = 4). These findings suggest that multiple, nonuniform mutation
s within the Ik gene are associated with acyclovir-resistant VZV pheno
types.