Correlation between viral resistance to zidovudine and resistance at the reverse transcriptase level for a panel of human immunodeficiency virus type 1 mutants

被引:45
作者
Lennerstrand, J
Hertogs, K
Stammers, DK
Larder, BA
机构
[1] Virco UK Ltd, Cambridge CB4 0GA, England
[2] Univ Oxford, Struct Biol Div, Wellcome Trust Ctr Human Genet, Oxford, England
[3] Virco NV, B-2800 Mechelen, Belgium
关键词
D O I
10.1128/JVI.75.15.7202-7205.2001
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Using a large panel of human immunodeficiency virus type 1 site-directed mutants, we have observed a higher correlation than has previously been demonstrated between zidovudine (AZT)-triphosphate resistance data at the reverse transcriptase (RT) level and corresponding viral AZT resistance. This enhanced-resistance effect at the RT level was seen with ATP and to a lesser extent with PP, when ATP was added at physiological concentrations. The ATP-dependent mechanism (analogous to pyrophosphorolysis) appears to be dominant in the mutants bearing the D67N and K70R or 69 insertion mutations, whereas the Q151M mutation seems independent of ATP for decreased binding to AZT-triphosphate.
引用
收藏
页码:7202 / 7205
页数:4
相关论文
共 26 条
[1]   Phenotypic mechanism of HIV-1 resistance to 3′-azido-3′-deoxythymidine (AZT):: Increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase [J].
Arion, D ;
Kaushik, N ;
McCormick, S ;
Borkow, G ;
Parniak, MA .
BIOCHEMISTRY, 1998, 37 (45) :15908-15917
[2]   LUMINESCENT IMMOBILIZED ENZYME TEST SYSTEMS FOR INORGANIC PYROPHOSPHATE - ASSAYS USING FIREFLY LUCIFERASE AND NICOTINAMIDE-MONONUCLEOTIDE ADENYLYL TRANSFERASE OR ADENOSINE-5'-TRIPHOSPHATE SULFURYLASE [J].
BARSHOP, BA ;
ADAMSON, DT ;
VELLOM, DC ;
ROSEN, F ;
EPSTEIN, BL ;
SEEGMILLER, JE .
ANALYTICAL BIOCHEMISTRY, 1991, 197 (01) :266-272
[3]   HIV POPULATION-DYNAMICS IN-VIVO - IMPLICATIONS FOR GENETIC-VARIATION, PATHOGENESIS, AND THERAPY [J].
COFFIN, JM .
SCIENCE, 1995, 267 (5197) :483-489
[4]  
Ekstrand DHL, 1996, BIOTECHNOL APPL BIOC, V23, P95
[5]   INFECTION OF HTLV-III/LAV IN HTLV-I-CARRYING CELLS MT-2 AND MT-4 AND APPLICATION IN A PLAQUE-ASSAY [J].
HARADA, S ;
KOYANAGI, Y ;
YAMAMOTO, N .
SCIENCE, 1985, 229 (4713) :563-566
[6]   Significance of amino acid variation at human immunodeficiency virus type 1 reverse transcriptase residue 210 for zidovudine susceptibility [J].
Harrigan, PR ;
Kinghorn, I ;
Bloor, S ;
Kemp, SD ;
Najera, I ;
Kohli, A ;
Larder, BA .
JOURNAL OF VIROLOGY, 1996, 70 (09) :5930-5934
[7]   Activities of cefepime and five other antibiotics against nosocomial PER-1-type and/or OXA-10-type β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter spp. -: J Antimicrob Chemother 1998; 42:269-270 [J].
Vahaboglu, H ;
Saribas, S ;
Akbal, H ;
Ozturk, R ;
Yucel, A .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1998, 42 (02) :269-270
[8]   5TH MUTATION IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE CONTRIBUTES TO THE DEVELOPMENT OF HIGH-LEVEL RESISTANCE TO ZIDOVUDINE [J].
KELLAM, P ;
BOUCHER, CAB ;
LARDER, BA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (05) :1934-1938
[9]   RECOMBINANT VIRUS ASSAY - A RAPID, PHENOTYPIC ASSAY FOR ASSESSMENT OF DRUG SUSCEPTIBILITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES [J].
KELLAM, P ;
LARDER, BA .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (01) :23-30
[10]   Single-step kinetics of HIV-1 reverse transcriptase mutants responsible for virus resistance to nucleoside inhibitors zidovudine and 3-TC [J].
Krebs, R ;
Immendorfer, U ;
Thrall, SH ;
Wohrl, BM ;
Goody, RS .
BIOCHEMISTRY, 1997, 36 (33) :10292-10300