title: Effect of the human immunodeficiency virus type 1 reverse transcriptase polymorphism Leu-214 on replication capacity and drug susceptibility.
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.
authors.affiliation: irsiCaixa Foundation, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Puertas
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Buzón
authors.forename: Anna
authors.initials: A
authors.lastname: Artese
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Luis
authors.initials: L
authors.lastname: Menendez-Arias
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007930:Leucine / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011110:Polymorphism, Genetic; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D015215:Zidovudine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D007930:Leucine