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 emergenceand phenotypic resistance of TAM1.
Autores: Puertas, M. C., Buzon, M. J., Artese, A., Alcaro, S., Menendez-Arias, L., Perno, C. F., Clotet, B., Ceccherini-Silberstein, F., and Martinez-Picado, J.