Blocking interactions between HIV-1 integrase and cellular cofactors: an emerging anti-retroviral strategy

Trends Pharmacol Sci. 2007 Oct;28(10):526-35. doi: 10.1016/j.tips.2007.09.005. Epub 2007 Sep 21.

Abstract

HIV-1 integrase (IN) executes the insertion of proviral DNA into the host cell genome, an essential step in the retroviral life cycle. This is a multi-step process that starts in the cytosol and culminates in the nucleus of the infected cell. It is becoming increasingly clear that IN interacts with a wide range of different host-cell proteins throughout the viral life cycle. These cellular cofactors are exploited for various functions, including nuclear import, DNA target-site selection and virion assembly. The disruption of key interactions between IN and direct cellular cofactors affords a novel therapeutic approach for the design and development of new classes of anti-retroviral agents. Here, we will discuss the rationale behind this emerging and promising therapeutic strategy for HIV drug discovery. Our discussion includes the identified IN cellular cofactors, key research developments in the field and the implications this approach will have on the current HIV treatment regimen.

Publication types

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

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Chaperonin 60 / antagonists & inhibitors
  • Chromosomal Proteins, Non-Histone / antagonists & inhibitors
  • DNA-Binding Proteins / antagonists & inhibitors
  • Drug Design*
  • HIV Integrase / drug effects*
  • HIV Integrase Inhibitors / pharmacology*
  • Intercellular Signaling Peptides and Proteins / physiology
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Polycomb Repressive Complex 2
  • RNA-Binding Proteins / antagonists & inhibitors
  • Repressor Proteins / antagonists & inhibitors
  • SMARCB1 Protein
  • Transcription Factors / antagonists & inhibitors
  • Uracil-DNA Glycosidase / antagonists & inhibitors
  • p300-CBP Transcription Factors / antagonists & inhibitors

Substances

  • Anti-HIV Agents
  • Chaperonin 60
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • EED protein, human
  • GEMIN2 protein, human
  • HIV Integrase Inhibitors
  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Repressor Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors
  • lens epithelium-derived growth factor
  • Polycomb Repressive Complex 2
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • HIV Integrase
  • Uracil-DNA Glycosidase
  • p31 integrase protein, Human immunodeficiency virus 1