Raltegravir and elvitegravir-resistance mutation E92Q affects HLA-B*40:02-restricted HIV-1-specific CTL recognition

Microbes Infect. 2014 May;16(5):434-8. doi: 10.1016/j.micinf.2014.03.003. Epub 2014 Mar 20.

Abstract

Interplay between drug-resistance mutations in CTL epitopes and HIV-1-specific CTLs may influence the control of HIV-1 viremia. However, the effect of integrase inhibitor (INI)-resistance mutations on the CTL recognition has not been reported. We here investigated the effect of a raltegravir and elvitegravir-resistance mutation (E92Q) on HLA-B*40:02-restricted Int92-102 (EL11: ETGQETAYFLL)-specific CTLs. EL11-specific CTLs recognized E92Q peptide-pulsed and E92Q mutant virus-infected cells less effectively than EL11 peptide-pulsed and wild-type virus-infected cells, respectively. Ex vivo ELISpot analysis showed no induction of E92Q-specific T cells in chronically HIV-1-infected individuals. Thus, we demonstrated that EL11-specific CTL recognition was affected by the INI-resistance mutation.

Keywords: CTL; HIV; Integrase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Drug Resistance, Viral
  • Enzyme-Linked Immunospot Assay
  • HIV Integrase / genetics
  • HIV Integrase / immunology*
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HLA-B Antigens / immunology*
  • Humans
  • Mutant Proteins / genetics
  • Mutant Proteins / immunology
  • Mutation, Missense*
  • Pyrrolidinones / pharmacology*
  • Quinolones / pharmacology*
  • Raltegravir Potassium
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Anti-HIV Agents
  • HLA-B Antigens
  • Mutant Proteins
  • Pyrrolidinones
  • Quinolones
  • Raltegravir Potassium
  • elvitegravir
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1