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

Abstract
We selected 39-azido-39-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 39-azido-29,39-dideoxyuridine and 39-azido-29,39-dideoxyguanosine but remained sensitive to several other inhibitors (29,39-dideoxyinosine, 29,39-dideoxy-29,39-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 59-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. Images

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