Phenotypic and genotypic characterization of acyclovir-resistant varicella-zoster viruses isolated from persons with AIDS.
Phenotypic and genotypic analyses were done on 17 varicella-zoster virus (VZV) isolates recovered from 10 persons with AIDS (mean CD4 cell count, 16.4/mm3) who had chronic VZV lesions. Eleven acyclovir-resistant isolates were recovered from 10 patients after a mean of 20.1 weeks 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 VZV isolates were deficient in thymidine kinase (TK) or induced a TK with altered substrate specificity; all isolates were susceptible to foscarnet. Ten of 11 acyclovir-resistant mutants contained tk gene mutations, including single nucleotide substitutions in highly conserved binding sites (n = 2) as well as nucleotide deletions (n = 4) and insertions (n = 4). These findings suggest that multiple, nonuniform mutations within the tk gene are associated with acyclovir-resistant VZV phenotypes.
Dept. of Laboratory Medicine and Pathology, Minneapolis, MN 55455-0392.
G
G
Boivin
C K
CK
Edelman
L
L
Pedneault
C L
CL
Talarico
K K
KK
Biron
H H
HH
Balfour
D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology*; D000212:Acyclovir / Q000494:pharmacology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D004279:DNA, Viral; D004352:Drug Resistance, Microbial; D005838:Genotype; D006562:Herpes Zoster / Q000150:complications* / Q000382:microbiology; D014645:Herpesvirus 3, Human / Q000187:drug effects / Q000201:enzymology / Q000302:isolation & purification*; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism
D004279:DNA, Viral; D013937:Thymidine Kinase; D000212:Acyclovir