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1型人类免疫缺陷病毒（HIV-1）和2型人类免疫缺陷病毒（HIV-2）逆转录酶中Glu-89残基的诱变：对核苷类似物耐药性的影响。

Mutagenesis of the Glu-89 residue in human immunodeficiency virus type 1 (HIV-1) and HIV-2 reverse transcriptases: effects on nucleoside analog resistance.

作者信息

Song Q, Yang G, Goff S P, Prasad V R

机构信息

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461-1602.

出版信息

J Virol. 1992 Dec;66(12):7568-71. doi: 10.1128/JVI.66.12.7568-7571.1992.

DOI:10.1128/JVI.66.12.7568-7571.1992
PMID:1279207
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC240471/
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.

摘要

先前研究表明，人类免疫缺陷病毒1型逆转录酶（RT）中的Glu-89突变为Gly会导致对几种双脱氧核苷类似物和膦甲酸（PFA；膦甲酸钠）产生耐药性。将该残基分别替换为Ala、Val、Ser、Thr、Gln、Asp、Asn或Lys，并检测突变型RTs对ddGTP和PFA的敏感性。用Ala、Gly、Val和Thr替换导致对ddGTP抑制产生耐药性，而氨基酸为Ser、Gln、Asn、Asp或Lys的突变体仅表现出中度耐药或无耐药性。PFA抑制实验得到了类似结果，只是Asp-89突变体也表现出耐药性。此外，将Glu-89突变为Gly引入人类免疫缺陷病毒2型的RT中同样使其对ddGTP和PFA均产生耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/240471/08ddaafbf59c/jvirol00043-0745-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/240471/08ddaafbf59c/jvirol00043-0745-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/240471/08ddaafbf59c/jvirol00043-0745-a.jpg

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