Mutagenesis of the Glu-89 residue in human immunodeficiency virus type 1 (HIV-1) and HIV-2 reverse transcriptases

Effects on nucleoside analog resistance

Qingbin Song, Guozhe Yang, Stephen P. Goff, Vinayaka R. Prasad

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

A Glu-89 → Gly alteration in the human immunodeficiency virus type 1 reverse transcriptase (RT) was previously shown to result in resistance to several dideoxynucleoside analogs and to phosphonoformic acid (PFA; foscarnet). This residue was altered to Ala, Val, Ser, Thr, Gln, Asp, Asn, or Lys, and the ddGTP and PFA sensitivities of the mutant RTs were measured. Replacements with Ala, Gly, Val, and Thr led to resistance to inhibition by ddGTP, while mutants with amino acid Ser, Gln, Asn, Asp, or Lys displayed only moderate or no resistance. A similar result was obtained with inhibition by PFA, except that the Asp-89 mutant also displayed resistance. Furthermore, the introduction of Glu-89 → Gly alteration into the RT of human immunodeficiency virus type 2 likewise rendered it resistant to both ddGTP and PFA.

Original languageEnglish (US)
Pages (from-to)7568-7571
Number of pages4
JournalJournal of Virology
Volume66
Issue number12
StatePublished - Dec 1992

Fingerprint

Human immunodeficiency virus 2
RNA-directed DNA polymerase
nucleosides
Human immunodeficiency virus 1
Nucleosides
mutagenesis
Mutagenesis
Foscarnet
HIV-1
mutants
Dideoxynucleosides
HIV-2
Viperidae
Amino Acids
amino acids
acids
Human immunodeficiency virus 2 reverse transcriptase
2',3'-dideoxyguanosine 5'-triphosphate

ASJC Scopus subject areas

  • Immunology

Cite this

Mutagenesis of the Glu-89 residue in human immunodeficiency virus type 1 (HIV-1) and HIV-2 reverse transcriptases : Effects on nucleoside analog resistance. / Song, Qingbin; Yang, Guozhe; Goff, Stephen P.; Prasad, Vinayaka R.

In: Journal of Virology, Vol. 66, No. 12, 12.1992, p. 7568-7571.

Research output: Contribution to journalArticle

@article{d2ebce377601469f8d308c654f6897f1,
title = "Mutagenesis of the Glu-89 residue in human immunodeficiency virus type 1 (HIV-1) and HIV-2 reverse transcriptases: Effects on nucleoside analog resistance",
abstract = "A Glu-89 → Gly alteration in the human immunodeficiency virus type 1 reverse transcriptase (RT) was previously shown to result in resistance to several dideoxynucleoside analogs and to phosphonoformic acid (PFA; foscarnet). This residue was altered to Ala, Val, Ser, Thr, Gln, Asp, Asn, or Lys, and the ddGTP and PFA sensitivities of the mutant RTs were measured. Replacements with Ala, Gly, Val, and Thr led to resistance to inhibition by ddGTP, while mutants with amino acid Ser, Gln, Asn, Asp, or Lys displayed only moderate or no resistance. A similar result was obtained with inhibition by PFA, except that the Asp-89 mutant also displayed resistance. Furthermore, the introduction of Glu-89 → Gly alteration into the RT of human immunodeficiency virus type 2 likewise rendered it resistant to both ddGTP and PFA.",
author = "Qingbin Song and Guozhe Yang and Goff, {Stephen P.} and Prasad, {Vinayaka R.}",
year = "1992",
month = "12",
language = "English (US)",
volume = "66",
pages = "7568--7571",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Mutagenesis of the Glu-89 residue in human immunodeficiency virus type 1 (HIV-1) and HIV-2 reverse transcriptases

T2 - Effects on nucleoside analog resistance

AU - Song, Qingbin

AU - Yang, Guozhe

AU - Goff, Stephen P.

AU - Prasad, Vinayaka R.

PY - 1992/12

Y1 - 1992/12

N2 - A Glu-89 → Gly alteration in the human immunodeficiency virus type 1 reverse transcriptase (RT) was previously shown to result in resistance to several dideoxynucleoside analogs and to phosphonoformic acid (PFA; foscarnet). This residue was altered to Ala, Val, Ser, Thr, Gln, Asp, Asn, or Lys, and the ddGTP and PFA sensitivities of the mutant RTs were measured. Replacements with Ala, Gly, Val, and Thr led to resistance to inhibition by ddGTP, while mutants with amino acid Ser, Gln, Asn, Asp, or Lys displayed only moderate or no resistance. A similar result was obtained with inhibition by PFA, except that the Asp-89 mutant also displayed resistance. Furthermore, the introduction of Glu-89 → Gly alteration into the RT of human immunodeficiency virus type 2 likewise rendered it resistant to both ddGTP and PFA.

AB - A Glu-89 → Gly alteration in the human immunodeficiency virus type 1 reverse transcriptase (RT) was previously shown to result in resistance to several dideoxynucleoside analogs and to phosphonoformic acid (PFA; foscarnet). This residue was altered to Ala, Val, Ser, Thr, Gln, Asp, Asn, or Lys, and the ddGTP and PFA sensitivities of the mutant RTs were measured. Replacements with Ala, Gly, Val, and Thr led to resistance to inhibition by ddGTP, while mutants with amino acid Ser, Gln, Asn, Asp, or Lys displayed only moderate or no resistance. A similar result was obtained with inhibition by PFA, except that the Asp-89 mutant also displayed resistance. Furthermore, the introduction of Glu-89 → Gly alteration into the RT of human immunodeficiency virus type 2 likewise rendered it resistant to both ddGTP and PFA.

UR - http://www.scopus.com/inward/record.url?scp=0026476308&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026476308&partnerID=8YFLogxK

M3 - Article

VL - 66

SP - 7568

EP - 7571

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 12

ER -