NOVEL MUTATION (V75T) IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE CONFERS RESISTANCE TO 2',3'-DIDEHYDRO-2',3'-DIDEOXYTHYMIDINE IN CELL-CULTURE

被引：122

作者：

LACEY, SF ^{[1
]}

LARDER, BA ^{[1
]}

机构：

[1] WELLCOME RES LABS,ANTIVIRAL THERAPEUT RES UNIT,BECKENHAM BR3 3BS,KENT,ENGLAND

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 1994年 / 38卷 / 06期

关键词：

D O I：

10.1128/AAC.38.6.1428

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

We have selected a human immunodeficiency virus type 1 (HIV-1) mutant strain with a moderate (sevenfold) level of resistance to the nucleoside analog 2',3'-didehydro-2',3'-dideoxythymidine (D4T or stavudine). After serial passage of the HXB2 strain of HIV-1 in MT4 cells, a novel mutation involving two nucleotide substitutions in codon 75 of the viral reverse transcriptase, altering valine to threonine, was seen. When introduced into a wild-type HIV-1 background by site-directed mutagenesis, the T-75 mutation conferred cross-resistance to the dideoxynucleosides dideoxyinosine and dideoxycytosine as well as to 2',3'-didehydro-2',3'-dideoxycytosine.

引用

页码：1428 / 1432

页数：5

共 29 条

[11]

LACEY SF, 1992, J BIOL CHEM, V267, P15789

[12] HIV WITH REDUCED SENSITIVITY TO ZIDOVUDINE (AZT) ISOLATED DURING PROLONGED THERAPY [J].

LARDER, BA ;

DARBY, G ;

RICHMAN, DD .

SCIENCE, 1989, 243 (4899) :1731-1734

[13] CONVERGENT COMBINATION THERAPY CAN SELECT VIABLE MULTIDRUG-RESISTANT HIV-1 IN-VITRO [J].

LARDER, BA ;

KELLAM, P ;

KEMP, SD .

NATURE, 1993, 365 (6445) :451-453

[14] ZIDOVUDINE RESISTANCE PREDICTED BY DIRECT DETECTION OF MUTATIONS IN DNA FROM HIV-INFECTED LYMPHOCYTES [J].

LARDER, BA ;

KELLAM, P ;

KEMP, SD .

AIDS, 1991, 5 (02) :137-144

[15] SUSCEPTIBILITIES OF ZIDOVUDINE-SUSCEPTIBLE AND ZIDOVUDINE-RESISTANT HUMAN-IMMUNODEFICIENCY-VIRUS ISOLATES TO ANTIVIRAL AGENTS DETERMINED BY USING A QUANTITATIVE PLAQUE REDUCTION ASSAY [J].

LARDER, BA ;

CHESEBRO, B ;

RICHMAN, DD .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1990, 34 (03) :436-441

[16] MULTIPLE MUTATIONS IN HIV-1 REVERSE-TRANSCRIPTASE CONFER HIGH-LEVEL RESISTANCE TO ZIDOVUDINE (AZT) [J].

LARDER, BA ;

KEMP, SD .

SCIENCE, 1989, 246 (4934) :1155-1158

[17]

LIN TS, 1987, BIOCHEM PHARMACOL, V36, P2713

[18]

MARTIN JC, 1990, ANN NY ACAD SCI, V616, P22

[19] MECHANISM OF RESISTANCE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TO 2',3'-DIDEOXYINOSINE [J].

MARTIN, JL ;

WILSON, JE ;

HAYNES, RL ;

FURMAN, PA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (13) :6135-6139

[20]

MYERS G, 1992, HUMAN RETROVIRUSES A

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