Implications of HIV-1 M Group Polymorphisms on Integrase Inhibitor Efficacy and Resistance: Genetic and Structural in Silico Analyses

被引：26

作者：

Loizidou, Eriketi Z. ^{[1
]}

Kousiappa, Ioanna ^{[1
]}

Zeinalipour-Yazdi, Constantinos D. ^{[2
]}

Van de Vijver, David A. M. C. ^{[3
]}

Kostrikis, Leondios G. ^{[1
]}

机构：

[1] Univ Cyprus, Dept Biol, CY-1678 Nicosia, Cyprus

[2] Univ Cyprus, Dept Chem, CY-1678 Nicosia, Cyprus

[3] Univ Med Ctr, Erasmus MC, Dept Virol, Rotterdam, Netherlands

来源：

BIOCHEMISTRY | 2009年 / 48卷 / 01期

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; RALTEGRAVIR; PROMOTES; PROTEASE; DOCKING; DOMAIN; VITRO;

D O I：

10.1021/bi8019349

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The extensive polymorphisms among HIV-1 subtypes have been implicated in drug resistance development. Integrase inhibitors represent the latest addition to the treatment of HIV-1, and their efficacy and resistance patterns among M group strains are currently under investigation. This study analyzed the intersubtype variation within 108 integrase sequences from seven subtypes. The residues associated with catalytic activity and primary resistance to raltegravir were highly conserved among all strains. Variations were observed in residues associated with secondary resistance. Molecular modeling studies indicated a two-way binding mode of raltegravir that explains the resistance pathways and the implication of nonconservative mutations in integrase-raltegravir interactions.

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页码：4 / 6

页数：3

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