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

被引:227
作者
GAO, Q
GU, ZX
PARNIAK, MA
CAMERON, J
CAMMACK, N
BOUCHER, C
WAINBERG, MA
机构
[1] SIR MORTIMER B DAVIS JEWISH HOSP,LADY DAVIS INST,3755 CHEMIN COTE ST CATHERINE,MONTREAL H3T 1E2,QUEBEC,CANADA
[2] MCGILL UNIV,AIDS CTR,MONTREAL H3A 2T5,QUEBEC,CANADA
[3] GLAXO GRP RES LTD,GREENFORD UB6 0HE,MIDDX,ENGLAND
[4] UNIV AMSTERDAM,ACAD MED CTR,DEPT MED MICROBIOL,1105 AZ AMSTERDAM,NETHERLANDS
关键词
D O I
10.1128/AAC.37.6.1390
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Variants of human immunodeficiency virus type 1 that display 500- to 1,000-fold resistance to the (-) enantiomer of 2'-deoxy-3'-thiacytidine and almost-equal-to 4- to 8-fold resistance to 2',3'-dideoxycytidine and 2',3'-dideoxyinosine have been generated through in vitro selection with the former compound. The polymerase regions of several of these resistant viruses shared a codon alteration at site 184 (ATG --> GTG; methionine --> valine), a mutation previously associated with low-level resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine. The biological relevance of this mutation for the (-) enantiomer of 2'-deoxy-3'-thiacytidine was confirmed by site-directed mutagenesis with the HXB2-D clone of human immunodeficiency virus type 1.
引用
收藏
页码:1390 / 1392
页数:3
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