Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes

Retrovirology. 2009 Nov 11:6:103. doi: 10.1186/1742-4690-6-103.

Abstract

Background: Integrase inhibitors are currently being incorporated into highly active antiretroviral therapy (HAART). Due to high HIV variability, integrase inhibitor efficacy must be evaluated against a range of integrase enzymes from different subtypes.

Methods: This study compares the enzymatic activities of HIV-1 integrase from subtypes B and C as well as susceptibility to various integrase inhibitors in vitro. The catalytic activities of both enzymes were analyzed in regard to each of 3' processing and strand transfer activities both in the presence and absence of the integrase inhibitors raltegravir (RAL), elvitegravir (EVG), and MK-2048.

Results: Our results show that integrase function is similar with enzymes of either subtype and that the various integrase strand transfer inhibitors (INSTIs) that were employed possessed similar inhibitory activity against both enzymes.

Conclusion: This suggests that the use of integrase inhibitors against HIV-1 subtype C will result in comparable outcomes to those obtained against subtype B infections.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Viral / metabolism
  • Genotype
  • HIV Integrase / metabolism*
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / classification
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • Inhibitory Concentration 50
  • Pyrrolidinones / pharmacology
  • Quinolones / pharmacology
  • Raltegravir Potassium

Substances

  • DNA, Viral
  • HIV Integrase Inhibitors
  • Pyrrolidinones
  • Quinolones
  • Raltegravir Potassium
  • elvitegravir
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1