Natural variation of HIV-1 group M integrase: Implications for a new class of antiretroviral inhibitors

被引:100
作者
Rhee, Soo-Yon [1 ]
Liu, Tommy F. [1 ]
Kiuchi, Mark [1 ]
Zioni, Rafael [1 ]
Gifford, Robert J. [1 ]
Holmes, Susan P. [2 ]
Shafer, Robert W. [1 ]
机构
[1] Stanford Univ, Dept Med, Div Infect Dis, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Stat, Stanford, CA 94305 USA
关键词
D O I
10.1186/1742-4690-5-74
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
HIV-1 integrase is the third enzymatic target of antiretroviral (ARV) therapy. However, few data have been published on the distribution of naturally occurring amino acid variation in this enzyme. We therefore characterized the distribution of integrase variants among more than 1,800 published group M HIV-1 isolates from more than 1,500 integrase inhibitor (INI)-naive individuals. Polymorphism rates equal or above 0.5% were found for 34% of the central core domain positions, 42% of the C-terminal domain positions, and 50% of the N-terminal domain positions. Among 727 ARV-naive individuals in whom the complete pol gene was sequenced, integrase displayed significantly decreased inter- and intra-subtype diversity and a lower Shannon's entropy than protease or RT. All primary INI-resistance mutations with the exception of E157Q - which was present in 1.1% of sequences - were nonpolymorphic. Several accessory INI-resistance mutations including L74M, T97A, V151I, G163R, and S230N were also polymorphic with polymorphism rates ranging between 0.5% to 2.0%.
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页数:11
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