A novel Met-to-Thr mutation in the YMDD motif of reverse transcriptase from feline immunodeficiency virus confers resistance to oxathiolane nucleosides

Robert A. Smith, Kathryn M. Remington, Robert M. Lloyd, Raymond F. Schinazi, Thomas W. North

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Variants of feline immunodeficiency virus (FIV) that possess a unique methionine-to-threonine mutation within the YMDD motif of reverse transcriptase (RT) were selected by culturing virus in the presence of inhibitory concentrations of (-)-β-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC]. The mutants were resistant to (-)-FTC and (-)-β-L-2',3'-dideoxy- 3'-thiacytidine (3TC) and additionally exhibited low-level resistance to 2',3'-dideoxycytidine (ddC). DNA sequence analysis of the RT-encoding region of the pol gene amplified from resistant viruses consistently identified a Met-to-Thr mutation in the YMDD motif. Purified RT from the mutants was also resistant to the 5'-triphosphate forms of 3TC, (-)-FTC, and ddC. Site- directed mutants of FIV were engineered which contain either the novel Met- to-Thr mutation or the Met-to-Val mutation seen in oxathiolane nucleoside- resistant HIV-1. Both site-directed mutants displayed resistance to 3TC, thus confirming the role of these mutations in the resistance of FIV to β-L-3'- thianucleosides.

Original languageEnglish (US)
Pages (from-to)2357-2362
Number of pages6
JournalJournal of Virology
Volume71
Issue number3
StatePublished - Mar 1997
Externally publishedYes

Fingerprint

Feline Immunodeficiency Virus
Feline immunodeficiency virus
RNA-directed DNA polymerase
nucleosides
RNA-Directed DNA Polymerase
Nucleosides
mutation
Mutation
Zalcitabine
mutants
pol Genes
Viruses
viruses
Lamivudine
Threonine
Human immunodeficiency virus 1
DNA Sequence Analysis
threonine
Methionine
HIV-1

ASJC Scopus subject areas

  • Immunology

Cite this

A novel Met-to-Thr mutation in the YMDD motif of reverse transcriptase from feline immunodeficiency virus confers resistance to oxathiolane nucleosides. / Smith, Robert A.; Remington, Kathryn M.; Lloyd, Robert M.; Schinazi, Raymond F.; North, Thomas W.

In: Journal of Virology, Vol. 71, No. 3, 03.1997, p. 2357-2362.

Research output: Contribution to journalArticle

Smith, Robert A. ; Remington, Kathryn M. ; Lloyd, Robert M. ; Schinazi, Raymond F. ; North, Thomas W. / A novel Met-to-Thr mutation in the YMDD motif of reverse transcriptase from feline immunodeficiency virus confers resistance to oxathiolane nucleosides. In: Journal of Virology. 1997 ; Vol. 71, No. 3. pp. 2357-2362.
@article{9cbd5cf48bad4fd1a34fd2b89622e675,
title = "A novel Met-to-Thr mutation in the YMDD motif of reverse transcriptase from feline immunodeficiency virus confers resistance to oxathiolane nucleosides",
abstract = "Variants of feline immunodeficiency virus (FIV) that possess a unique methionine-to-threonine mutation within the YMDD motif of reverse transcriptase (RT) were selected by culturing virus in the presence of inhibitory concentrations of (-)-β-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC]. The mutants were resistant to (-)-FTC and (-)-β-L-2',3'-dideoxy- 3'-thiacytidine (3TC) and additionally exhibited low-level resistance to 2',3'-dideoxycytidine (ddC). DNA sequence analysis of the RT-encoding region of the pol gene amplified from resistant viruses consistently identified a Met-to-Thr mutation in the YMDD motif. Purified RT from the mutants was also resistant to the 5'-triphosphate forms of 3TC, (-)-FTC, and ddC. Site- directed mutants of FIV were engineered which contain either the novel Met- to-Thr mutation or the Met-to-Val mutation seen in oxathiolane nucleoside- resistant HIV-1. Both site-directed mutants displayed resistance to 3TC, thus confirming the role of these mutations in the resistance of FIV to β-L-3'- thianucleosides.",
author = "Smith, {Robert A.} and Remington, {Kathryn M.} and Lloyd, {Robert M.} and Schinazi, {Raymond F.} and North, {Thomas W.}",
year = "1997",
month = "3",
language = "English (US)",
volume = "71",
pages = "2357--2362",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - A novel Met-to-Thr mutation in the YMDD motif of reverse transcriptase from feline immunodeficiency virus confers resistance to oxathiolane nucleosides

AU - Smith, Robert A.

AU - Remington, Kathryn M.

AU - Lloyd, Robert M.

AU - Schinazi, Raymond F.

AU - North, Thomas W.

PY - 1997/3

Y1 - 1997/3

N2 - Variants of feline immunodeficiency virus (FIV) that possess a unique methionine-to-threonine mutation within the YMDD motif of reverse transcriptase (RT) were selected by culturing virus in the presence of inhibitory concentrations of (-)-β-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC]. The mutants were resistant to (-)-FTC and (-)-β-L-2',3'-dideoxy- 3'-thiacytidine (3TC) and additionally exhibited low-level resistance to 2',3'-dideoxycytidine (ddC). DNA sequence analysis of the RT-encoding region of the pol gene amplified from resistant viruses consistently identified a Met-to-Thr mutation in the YMDD motif. Purified RT from the mutants was also resistant to the 5'-triphosphate forms of 3TC, (-)-FTC, and ddC. Site- directed mutants of FIV were engineered which contain either the novel Met- to-Thr mutation or the Met-to-Val mutation seen in oxathiolane nucleoside- resistant HIV-1. Both site-directed mutants displayed resistance to 3TC, thus confirming the role of these mutations in the resistance of FIV to β-L-3'- thianucleosides.

AB - Variants of feline immunodeficiency virus (FIV) that possess a unique methionine-to-threonine mutation within the YMDD motif of reverse transcriptase (RT) were selected by culturing virus in the presence of inhibitory concentrations of (-)-β-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC]. The mutants were resistant to (-)-FTC and (-)-β-L-2',3'-dideoxy- 3'-thiacytidine (3TC) and additionally exhibited low-level resistance to 2',3'-dideoxycytidine (ddC). DNA sequence analysis of the RT-encoding region of the pol gene amplified from resistant viruses consistently identified a Met-to-Thr mutation in the YMDD motif. Purified RT from the mutants was also resistant to the 5'-triphosphate forms of 3TC, (-)-FTC, and ddC. Site- directed mutants of FIV were engineered which contain either the novel Met- to-Thr mutation or the Met-to-Val mutation seen in oxathiolane nucleoside- resistant HIV-1. Both site-directed mutants displayed resistance to 3TC, thus confirming the role of these mutations in the resistance of FIV to β-L-3'- thianucleosides.

UR - http://www.scopus.com/inward/record.url?scp=0031047825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031047825&partnerID=8YFLogxK

M3 - Article

VL - 71

SP - 2357

EP - 2362

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 3

ER -