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 language | English (US) |
|---|---|
| Pages (from-to) | 2357-2362 |
| Number of pages | 6 |
| Journal | Journal of Virology |
| Volume | 71 |
| Issue number | 3 |
| State | Published - Mar 1997 |
| Externally published | Yes |
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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 journal › Article
}
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.
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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 -