Effect of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Polymorphism Leu-214 on Replication Capacity and Drug Susceptibility

被引：12

作者：

Carmen Puertas, Maria ^{[1
]}

Jose Buzon, Maria ^{[1
]}

Artese, Anna ^{[2
]}

Alcaro, Stefano ^{[2
]}

Menendez-Arias, Luis ^{[3
,4
]}

Perno, Carlo Federico ^{[5
]}

Clotet, Bonaventura ^{[1
]}

Ceccherini-Silberstein, Francesca ^{[5
]}

Martinez-Picado, Javier ^{[1
,6
]}

机构：

[1] IrsiCaixa Fdn, Hosp Germans Trias & Pujol, Badalona 08916, Spain

[2] Univ Catanzaro Magna Graecia, Dept Pharmacobiol Sci, Catanzaro, Italy

[3] CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain

[4] Univ Autonoma Madrid, Madrid, Spain

[5] Univ Roma Tor Vergata, Dept Expt Med, Rome, Italy

[6] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain

来源：

JOURNAL OF VIROLOGY | 2009年 / 83卷 / 15期

关键词：

RESISTANCE MUTATIONS; ANTIRETROVIRAL THERAPY; ZIDOVUDINE RESISTANCE; VIROLOGICAL RESPONSE; EXPERIENCED PATIENTS; COMBINATION THERAPY; IN-VITRO; HIV-1; PATTERNS; INHIBITORS;

D O I：

10.1128/JVI.00487-09

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

A negative association between polymorphism Leu-214 and type-1 thymidine analogue mutations (TAM1) and a positive association with a clinically favorable virological response to thymidine analogue-based combination antiretroviral therapy have been described. In this study, the impact of Leu-214 on replication capacity and resistance to zidovudine (ZDV) of viruses containing TAM1 or TAM2 was determined. Leu-214 decreased the growth rate of viruses bearing Tyr-215, as well as their resistance to ZDV. This observation was confirmed by structural and molecular modeling data, suggesting a regulatory role for Leu-214 in the emergence and phenotypic resistance of TAM1.

引用

页码：7434 / 7439

页数：6

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