We have selected and plaque purified a mutant of feline immunodeficiency virus (FIV) that is resistant to 2′,3′-dideoxycytidine (ddC). This mutant was selected in cultured cells in the continuous presence of 25 μM ddC. The mutant, designated DCR-5c, was fourfold resistant to ddC, threefold resistant to 2′,3′-dideoxyinosine, and more than fourfold resistant to phosphonoformic acid. DCR-5c displayed little or no resistance to (-)-β-2′,3′-dideoxy-3′-thiacytidine, 3′-azido-3′-deoxythymidine, or 9-(2-phosphonylmethoxyethyl)adenine. Reverse transcriptase purified from DCR-5c was less susceptible to inhibition by ddCTP, phosphonoformic acid, ddATP, or azido-dTTP than the wild-type FIV reverse transcriptase. Sequence analysis of DCR-5c revealed a single base change (G to C at nucleotide 2342) in the reverse transcriptase-encoding region of FIV. This mutation results in substitution of His for Asp at codon 3 of FIV reverse transcriptase. The role of this mutation in ddC resistance was confirmed by site-directed mutagenesis.
|Original language||English (US)|
|Number of pages||5|
|Journal||Antimicrobial Agents and Chemotherapy|
|State||Published - Apr 1996|
ASJC Scopus subject areas
- Pharmacology (medical)