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Journal of Virology, August 2009, p. 7434-7439, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00487-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Maria Carmen Puertas,1 Maria Jose Buzón,1 Anna Artese,2 Stefano Alcaro,2 Luis Menendez-Arias,3 Carlo Federico Perno,4 Bonaventura Clotet,1 Francesca Ceccherini-Silberstein,4,{dagger} and Javier Martinez-Picado1,5*,{dagger}

irsiCaixa Foundation, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain,1 Department of Pharmacobiological Sciences, University of Catanzaro Magna Graecia, Catanzaro, Italy,2 Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain,3 Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy,4 Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain5

Received 9 March 2009/ Accepted 14 May 2009

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.

* Corresponding author. Mailing address: irsiCaixa Foundation, Hospital Germans Trias i Pujol, Ctra. de Canyet s/n, 08916 Badalona, Spain. Phone: 34 934656374. Fax: 34 934653968. E-mail: jmpicado{at}irsicaixa.es

{triangledown} Published ahead of print on 20 May 2009.

{dagger} F.C.-S. and J.M.-P. contributed equally to this study.

Journal of Virology, August 2009, p. 7434-7439, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00487-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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