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Effect of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Polymorphism Leu-214 on Replication Capacity and Drug Susceptibility
Author(s) -
María C. Puertas,
María J. Buzón,
Anna Artese,
Stefano Alcaro,
Luis MenéndezArias,
Carlo Federico Perno,
Bonaventura Clotet,
Francesca CeccheriniSilberstein,
Javier MartínezPicado
Publication year - 2009
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.00487-09
Subject(s) - zidovudine , biology , reverse transcriptase , virology , thymidine , drug resistance , genotype , viral replication , polymorphism (computer science) , phenotype , virus , genetics , viral disease , in vitro , polymerase chain reaction , gene
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.

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