Characterization of a DNA polymerase mutant of herpes simplex virus from a severely immunocompromised patient receiving acyclovir.
A series of herpes simplex virus isolates were recovered from a bone marrow transplant patient who received prolonged acyclovir therapy for indolent herpes simplex mouth and throat ulceration. Of 14 isolates received 10 were resistant to acyclovir and partially resistant to phosphonoacetic acid. Biochemical characterization revealed that resistance was due to an alteration in the virus DNA polymerase. DNA sequence analysis of the polymerase gene of a plaque-purified resistant virus isolate revealed a single nucleotide change when compared with the sequence of the gene of a plaque-purified sensitive isolate. This single base change resulted in a predicted amino acid substitution of Gly to Ser at residue number 841, a putative functional region of the polymerase.
Collins
P
P
Department of Molecular Sciences, Wellcome Research Laboratories, Beckenham, Kent, U.K.
Larder
B A
BA
Oliver
N M
NM
Kemp
S
S
Smith
I W
IW
Darby
G
G
D000212:Acyclovir / Q000627:therapeutic use*; D000328:Adult; D001483:Base Sequence; D001853:Bone Marrow / Q000382:microbiology; D016026:Bone Marrow Transplantation; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D004352:Drug Resistance, Microbial; D005260:Female; D005814:Genes, Viral; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000382:microbiology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000382:microbiology / Q000628:therapy; D009154:Mutation; D018139:Simplexvirus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D013283:Stomatitis, Herpetic / Q000188:drug therapy / Q000382:microbiology
D004259:DNA-Directed DNA Polymerase; D000212:Acyclovir