Multiple-drug-resistant mutants of feline immunodeficiency virus selected with 2',3'-dideoxyinosine alone and in combination with 3'-azido-3'-deoxythymidine.
Mutants of feline immunodeficiency virus (FIV) were selected in cell culture in the continuous presence of 10 microM (each) 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI). These mutants (AIR-1 and AIR-3) displayed a 13-fold resistance to AZT but had less than a 2-fold decrease in susceptibility to ddI. Interestingly, the AIR mutants were cross-resistant to phosphonoformate (PFA) and were hypersensitive to 2',3'-dideoxycytidine (ddC). Mutants of FIV were also selected in the presence of 10 microM ddI alone (DIS-1, DIS-2c), and these displayed a two- to fourfold decrease in susceptibility to ddI. Like the mutants selected with the combination of AZT plus ddI, DIS-1 and DIS-2c were cross-resistant to PFA and were hypersensitive to ddC. However, they remained as susceptible as wild-type FIV to AZT. Thus, the mutants selected with the combination of AZT plus ddI have phenotypes which reflect those obtained by selection with these drugs individually.
Division of Biological Sciences, University of Montana, Missoula 59812.
J M
JM
Gobert
K M
KM
Remington
Y Q
YQ
Zhu
T W
TW
North
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002415:Cats; D002478:Cells, Cultured; D016049:Didanosine / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D017245:Foscarnet / Q000494:pharmacology; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects* / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D016047:Zalcitabine / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology*
D000998:Antiviral Agents; D017245:Foscarnet; D015215:Zidovudine; D016047:Zalcitabine; D016049:Didanosine