A ganciclovir-resistant clinical isolate of human cytomegalovirus exhibiting cross-resistance to other DNA polymerase inhibitors.
Clinical isolates of human cytomegalovirus (HCMV) were screened for susceptibility to ganciclovir by plaque-reduction assay and in situ ELISA. A pretreatment isolate of HCMV obtained from the bronchial brushing of a heart transplant recipient contained both ganciclovir-susceptible and -resistant virus. Ganciclovir-susceptible (P8) and -resistant (D16) strains were further isolated by plaque purification. Both strains phosphorylated ganciclovir at levels similar to the ganciclovir-susceptible strain AD169. D16 was also resistant to phosphonoformic acid and to (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and cytosine. These data suggest that the resistance of D16 to these drugs results from a mutation in the viral DNA polymerase gene.
Tatarowicz
W A
WA
Department of Microbiology, Loyola University Medical Center, Maywood, Illinois 60153.
Lurain
N S
NS
Thompson
K D
KD
D000998:Antiviral Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003587:Cytomegalovirus / Q000187:drug effects* / Q000254:growth & development; D004352:Drug Resistance, Microbial; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D017245:Foscarnet; D015774:Ganciclovir / Q000494:pharmacology*; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010948:Viral Plaque Assay / Q000379:methods
D000998:Antiviral Agents; D019384:Nucleic Acid Synthesis Inhibitors; D017245:Foscarnet; D010746:Phosphonoacetic Acid; D015774:Ganciclovir