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
收藏
页码：7434 / 7439
页数：6
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