Characterization of the DNA polymerase and thymidine kinase genesof herpes simplex virus isolates from AIDS patients in whom acyclovirand foscarnet therapy sequentially failed.
Herpes simplex virus (HSV) isolates were characterized from 8 AIDS patients in whom acyclovir and foscarnet therapy sequentially failed. The 6 postacyclovir (prefoscarnet) HSV isolates were resistant to acyclovir and susceptible to foscarnet. Of the 9 postfoscarnet isolates, 8 were foscarnet-resistant and acyclovir-susceptible, 1 was resistant to both drugs. Acyclovir- or foscarnet-resistant isolates retained susceptibility to cidofovir. The acyclovir-resistant isolates contained single-base substitutions or frameshift mutations in G or C homopolymer nucleotide repeats of the thymidine kinase gene. In contrast, the foscarnet-resistant strains contained single-base substitutions in conserved (II, III, or VI) or, more rarely, nonconserved (between I and VII) regions of the DNA polymerase (pol) gene. The single isolate exhibiting resistance to acyclovir and foscarnet contained mutations in both genes. In this study of clinical HSV isolates, DNA pol mutations conferring foscarnet resistance were not associated with decreased acyclovir or cidofovir susceptibility.
Schmit
I
I
Infectious Disease Research Center, Centre Hospitalier de l'Université Laval, Québec, Canada, G1V 4G2. isabelle_schmit@hotmail.com
Boivin
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G
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000821:virology*; D000212:Acyclovir / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000235:genetics; D017245:Foscarnet / Q000494:pharmacology / Q000627:therapeutic use; D015684:Gene Products, pol / Q000235:genetics; D006561:Herpes Simplex / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D018139:Simplexvirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D017211:Treatment Failure
D000998:Antiviral Agents; D015684:Gene Products, pol; D017245:Foscarnet; D013937:Thymidine Kinase; D004259:DNA-Directed DNA Polymerase; D000212:Acyclovir