A mutation in the 3′ region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance

被引：36

作者：

Harrigan, PR

Salim, M

Stammers, DK

Wynhoven, B

Brumme, ZL

McKenna, P

Larder, B

Kemp, SD

机构：

[1] BC Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada

[2] Virco United Kingdom Ltd, Cambridge, England

[3] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[4] Virco NV, Mechelen, Belgium

来源：

JOURNAL OF VIROLOGY | 2002年 / 76卷 / 13期

关键词：

D O I：

10.1128/JVI.76.13.6836-6840.2002

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The Y318F substitution in the 3' region of human immunodeficiency virus type I (HIV-1) reverse transcriptase (RT) has been linked to normucleoside RT inhibitor (NNRTI) resistance in vitro. A systematic search of a large phenotypic-genotypic database (Virco) linked the Y318F substitution with a >10-fold decrease in NNRTI susceptibility in >85% of clinically derived isolates. There was a significant association between Y318F and use of delavirdine (P = 10(-11)) and nevirapine (P = 10(-6)) but not efavirenz (P = 0.3). Site-directed HIV-1 Y318F mutants in an HXB2 background displayed 42-fold-decreased susceptibility to delavirdine but <3-fold-decreased susceptibility to nevirapine or efavirenz. Combinations of Y318F with K103N, Y181C, or both resulted in decreased efavirenz susceptibility of 43-, 3.3-, and 84-fold, respectively, as well as >100- and >60-fold decreases in delavirdine and nevirapine susceptibility, respectively. These results indicate the importance of the Y318F substitution in HIV-1 drug resistance.

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页码：6836 / 6840

页数：5

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