Genetic characterization of thymidine kinase from acyclovir-resistant and -susceptible herpes simplex virus type 1 isolated from bone marrow transplant recipients.
Emergence of acyclovir (Acy)-resistant herpes simplex virus (HSV) is a major concern in bone marrow transplant recipients. Phenotypic and genetic characterization of thymidine kinase (TK) was done for 7 Acy-susceptible and 11 Acy-resistant HSV-1 isolated from 11 patients. In total, 19 amino acid substitutions were detected that were not related to Acy resistance but to TK gene polymorphism, including 5 mutations that have not been previously reported. The Acy-resistant strain from 1 patient presented no TK gene mutation related to resistance. Five patients (45%) had isolates that harbored point mutations leading to amino acid substitutions that could be associated with Acy resistance. Of the 5 substitutions detected, 3 have not been previously reported (codons 51, 83, and 175). A nucleotide insertion or deletion was detected in resistant isolates from 5 patients (45%); these mutations are located in homopolymer repeats at codon 92 (1 subject) and at codon 146 (4 subjects).
Morfin
F
F
Laboratory of Virology of the Hospices Civils de Lyon, Domaine Rockefeller, 69373 Lyon Cedex 08, France. fmorfin@rockefeller. univ-lyon1.fr
Souillet
G
G
Bilger
K
K
Ooka
T
T
Aymard
M
M
Thouvenot
D
D
D000212:Acyclovir / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D004352:Drug Resistance, Microbial / Q000235:genetics; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D013937:Thymidine Kinase / Q000235:genetics*
D000998:Antiviral Agents; D013937:Thymidine Kinase; D000212:Acyclovir