Mutants of feline immunodeficiency virus resistant to 3'-azido-3'-deoxythymidine

We selected 3'-azido-3'-deoxythymidine (AZT)-resistant mutants of feline immunodeficiency virus (FIV) in a cat cell culture system. The characterization of one of these mutants was facilitated by the development of a focal immunoassay which could accurately measure FIV infectivity. This assay was used to quantitate the susceptibility of FIV to various inhibitors. The AZT-resistant mutant was found to be cross-resistant to 3'-azido-2',3'-dideoxyuridine and 3'-azido-2',3'-dideoxyguanosine but remained sensitive to several other inhibitors (2',3'-dideoxyinosine, 2',3'-dideoxy-2',3'-didehydrothymidine, and phosphonoformate). These patterns of cross-resistance and sensitivity were similar to those of the AZT-resistant human immunodeficiency virus (HIV) that has recently been isolated from patients with AIDS (B. A. Larder and S. D. Kemp, Science 246:1155-1158, 1989). Like the AZT-resistant HIV, purified reverse transcriptase from mutant FIV failed to show resistance to the 5'-triphosphate of AZT. This mutant can be used in the FIV model system to study the mechanisms of drug resistance and to determine the pathogenicity of AZT-resistant mutants.