Effect of the human immunodeficiency virus type 1 reverse transcriptase polymorphism Leu-214 on replication capacity and drug susceptibility

J Virol. 2009 Aug;83(15):7434-9. doi: 10.1128/JVI.00487-09. Epub 2009 May 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Drug Resistance, Viral*
  • HIV Infections / virology*
  • HIV Reverse Transcriptase / genetics*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • HIV-1 / physiology
  • Humans
  • Leucine / genetics*
  • Leucine / metabolism
  • Mutation
  • Polymorphism, Genetic*
  • Virus Replication / drug effects*
  • Zidovudine / pharmacology

Substances

  • Anti-HIV Agents
  • Zidovudine
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • Leucine