A point mutation within a distinct conserved region of the herpes simplex virus DNA polymerase gene confers drug resistance.
We have shown that a drug-resistant mutant from a clinical isolate of herpes simplex virus contains a single point mutation in the DNA polymerase gene that confers resistance to both acyclovir and foscarnet. The mutated amino acid is located within a distinct conserved region shared among alpha-like DNA polymerases which we designate region VII. We infer that these conserved sequences are directly or indirectly involved in the recognition and binding of nucleotide and PPi substrates.
Hwang
C B
CB
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
Ruffner
K L
KL
Coen
D M
DM
D000212:Acyclovir / Q000494:pharmacology; D000595:Amino Acid Sequence; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D004352:Drug Resistance, Microbial; D017245:Foscarnet; D005814:Genes, Viral; D008969:Molecular Sequence Data; D009154:Mutation; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016415:Sequence Alignment; D018139:Simplexvirus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D014443:Tyrosine / Q000737:chemistry; D015678:Viral Structural Proteins / Q000235:genetics
D015678:Viral Structural Proteins; D017245:Foscarnet; D014443:Tyrosine; D004259:DNA-Directed DNA Polymerase; D010746:Phosphonoacetic Acid; D000212:Acyclovir