Ganciclovir-resistant cytomegalovirus clinical isolates: mode of resistance to ganciclovir.
Cytomegalovirus strains with reduced in vitro susceptibilities to ganciclovir have been recovered from patients who failed long-term ganciclovir therapy. The ganciclovir-resistant clinical isolates in this study were unable to induce ganciclovir phosphorylation in virus-infected cells. The viral DNA polymerase function appeared unaltered in one genetically pure ganciclovir-resistant strain, compared with that of its wild-type ganciclovir-sensitive counterpart. All nine of the ganciclovir-resistant strains were susceptible to foscarnet. Moreover, these strains were sensitive to inhibition both by vidarabine and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC), antiviral agents that are activated by cellular enzymes, and by (S)-1(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), which is a monophosphate nucleoside analog. The in vitro resistance to ganciclovir of the ganciclovir-resistant clinical isolates studied was attributed to the inability of the cells infected with these isolates to phosphorylate ganciclovir; the virally encoded DNA polymerase did not appear to play a role in this ganciclovir resistance.
Stanat
S C
SC
Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
Reardon
J E
JE
Erice
A
A
Jordan
M C
MC
Drew
W L
WL
Biron
K K
KK
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000998:Antiviral Agents / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects*; D003586:Cytomegalovirus Infections / Q000150:complications / Q000382:microbiology; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis; D004259:DNA-Directed DNA Polymerase / Q000302:isolation & purification; D004352:Drug Resistance, Microbial; D015774:Ganciclovir / Q000494:pharmacology*; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D004279:DNA, Viral; D019384:Nucleic Acid Synthesis Inhibitors; D004259:DNA-Directed DNA Polymerase; D015774:Ganciclovir