JVI Accepts, published online ahead of print on 20 May 2009
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J. Virol. doi:10.1128/JVI.00487-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Effect of the HIV-1 Reverse Transcriptase Polymorphism Leu-214 on Replication Capacity and Drug Susceptibility

Maria Carmen Puertas, Maria Jose Buzón, Anna Artese, Stefano Alcaro, Luis Menendez-Arias, Carlo Federico Perno, Bonaventura Clotet, Francesca Ceccherini-Silberstein, and Javier Martinez-Picado*

irsiCaixa Foundation, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; Department of Pharmacobiological Sciences, University of Catanzaro Magna Græcia, Catanzaro, Italy; Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain; Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain

* To whom correspondence should be addressed. Email: jmpicado{at}irsicaixa.es.


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Abstract

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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