Selection and characterization of a mutant of feline immunodeficiency virus resistant to 2′ ,3 ′ -dideoxycytidine

Holly K. Medlin, Ya Qi Zhu, Kathryn M. Remington, Tom R. Phillips, Thomas W. North

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)953-957
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume40
Issue number4
StatePublished - Apr 1996
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology (medical)

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    Medlin, H. K., Zhu, Y. Q., Remington, K. M., Phillips, T. R., & North, T. W. (1996). Selection and characterization of a mutant of feline immunodeficiency virus resistant to 2′ ,3 ′ -dideoxycytidine. Antimicrobial Agents and Chemotherapy, 40(4), 953-957.