Effect of the human immunodeficiency virus type 1 reverse transcriptase polymorphism Leu-214 on replication capacity and drug susceptibility.
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.
Puertas
Maria Carmen
MC
irsiCaixa Foundation, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
Buzón
Maria Jose
MJ
Artese
Anna
A
Alcaro
Stefano
S
Menendez-Arias
Luis
L
Perno
Carlo Federico
CF
Clotet
Bonaventura
B
Ceccherini-Silberstein
Francesca
F
Martinez-Picado
Javier
J
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
D019380:Anti-HIV Agents; D015215:Zidovudine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D007930:Leucine