Endogenous reverse transcription assays reveal high-level resistance to the triphosphate of (-)2'-dideoxy-3'-thiacytidine by mutated M184V human immunodeficiency virus type 1

被引:44
作者
Quan, YD
Gu, ZX
Li, XG
Li, Z
Morrow, CD
Wainberg, MA
机构
[1] MCGILL UNIV,DEPT MED,MONTREAL,PQ,CANADA
[2] MCGILL UNIV,DEPT MICROBIOL,MONTREAL,PQ H3A 2T5,CANADA
[3] UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294
关键词
D O I
10.1128/JVI.70.8.5642-5645.1996
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Kinetic analysis showed that the K-i values and the K-i/K-m ratios for mutated, recombinant M184V human immunodeficiency virus type 1 reverse transcriptase (RT) for (-)2'-dideoxy-3'-thiacytidine triphosphate (3TCTP) were 35-fold higher than the equivalent values for wild-type RT but only about twice as high as the equivalent values for each of the triphosphates of ddC (ddCTP) and ddA (ddATP). Fully endogenous RT assays showed that viruses containing the M184V substitution were highly resistant to 3TCTP, with an increase in the 50% inhibitory concentration of 250-fold in comparison with wild-type recombinant virus.
引用
收藏
页码:5642 / 5645
页数:4
相关论文
共 24 条
[1]   TRANSACTIVATION OF THE MINUS-STRAND DNA TRANSFER BY NUCLEOCAPSID PROTEIN DURING REVERSE TRANSCRIPTION OF THE RETROVIRAL GENOME [J].
ALLAIN, B ;
LAPADATTAPOLSKY, M ;
BERLIOZ, C ;
DARLIX, JL .
EMBO JOURNAL, 1994, 13 (04) :973-981
[2]  
ARTS EJ, 1994, J BIOL CHEM, V269, P14672
[3]   DEVELOPMENT OF A HUMAN IMMUNODEFICIENCY VIRUS-1 IN-VITRO DNA-SYNTHESIS SYSTEM TO STUDY REVERSE-TRANSCRIPTASE INHIBITORS [J].
BORROTOESODA, K ;
BOONE, LR .
ANTIVIRAL RESEARCH, 1994, 23 (3-4) :235-249
[4]   CASSETTE MUTAGENESIS OF THE REVERSE-TRANSCRIPTASE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 [J].
BOYER, PL ;
FERRIS, AL ;
HUGHES, SH .
JOURNAL OF VIROLOGY, 1992, 66 (02) :1031-1039
[5]   ANALYSIS OF MUTATIONS AT POSITION-184 IN REVERSE-TRANSCRIPTASE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 [J].
BOYER, PL ;
HUGHES, SH .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1995, 39 (07) :1624-1628
[6]   A 2ND ORIGIN OF DNA PLUS-STRAND SYNTHESIS IS REQUIRED FOR OPTIMAL HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION [J].
CHARNEAU, P ;
ALIZON, M ;
CLAVEL, F .
JOURNAL OF VIROLOGY, 1992, 66 (05) :2814-2820
[7]   CIS ELEMENTS AND TRANS-ACTING FACTORS INVOLVED IN THE RNA DIMERIZATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS HIV-1 [J].
DARLIX, JL ;
GABUS, C ;
NUGEYRE, MT ;
CLAVEL, F ;
BARRESINOUSSI, F .
JOURNAL OF MOLECULAR BIOLOGY, 1990, 216 (03) :689-699
[8]  
DEBYSER Z, 1992, J BIOL CHEM, V267, P11769
[9]   INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE BY THE 5'-TRIPHOSPHATE-BETA ENANTIOMERS OF CYTIDINE ANALOGS [J].
FARAJ, A ;
AGROFOGLIO, LA ;
WAKEFIELD, JK ;
MCPHERSON, S ;
MORROW, CD ;
GOSSELIN, G ;
MATHE, C ;
IMBACH, JL ;
SCHINAZI, RF ;
SOMMADOSSI, JP .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (10) :2300-2305
[10]   THE SAME MUTATION THAT ENCODES LOW-LEVEL HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RESISTANCE TO 2',3'-DIDEOXYINOSINE AND 2',3'-DIDEOXYCYTIDINE CONFERS HIGH-LEVEL RESISTANCE TO THE (-) ENANTIOMER OF 2',3'-DIDEOXY-3'-THIACYTIDINE [J].
GAO, Q ;
GU, ZX ;
PARNIAK, MA ;
CAMERON, J ;
CAMMACK, N ;
BOUCHER, C ;
WAINBERG, MA .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1993, 37 (06) :1390-1392