A novel point mutation at position 156 of reverse transcriptase from feline immunodeficiency virus confers resistance to the combination of (-)- β-2',3'-dideoxy-3'-thiacytidine and 3'-azido-3'-deoxythymidine

Robert A. Smith, Kathryn M. Remington, Bradley D. Preston, Raymond F. Schinazi, Thomas W. North

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Mutants of feline immunodeficiency virus (FIV) resistant to (-)-β- 2',3'-dideoxy-3'-thiacytidine (3TC) were selected by culturing virus in the presence of increasing stepwise concentrations of 3TC. Two plaque-purified variants were isolated from the original mutant population, and both of these mutants were resistant to 3TC. Surprisingly, these mutants were also phenotypically resistant to 3'-azido-3'-deoxythymidine (AZT) and to the combination of 3TC and AZT. Purified reverse transcriptase (RT) from one of these plaque-purified mutants was resistant to the 5'-triphosphates of 3TC and AZT. DNA sequence analysis of the RT-encoding region of the pol gene amplified from the plaque-purified mutants revealed a Pro-to-Ser mutation at position 156 of RT. A site-directed mutant of FTV engineered to contain this Pro-156-Ser mutation was resistant to 3TC, AZT, and the combination of 3TC and AZT, confirming the role of the Pro-156-Ser mutation in the resistance of FIV to these two nucleoside analogs. This represents the first report of a lentiviral mutant resistant to the combination of AZT and 3TC due to a single, unique point mutation.

Original languageEnglish (US)
Pages (from-to)2335-2340
Number of pages6
JournalJournal of Virology
Volume72
Issue number3
StatePublished - Mar 1998

ASJC Scopus subject areas

  • Immunology

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