Blocking interactions between HIV-1 integrase and cellular cofactors: an emerging anti-retroviral strategy.
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.
Al-Mawsawi
Laith Q
LQ
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90089, USA.
Neamati
Nouri
N
D019380:Anti-HIV Agents / Q000494:pharmacology*; D018834:Chaperonin 60 / Q000037:antagonists & inhibitors; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D015195:Drug Design; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D063151:Polycomb Repressive Complex 2; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors; D012097:Repressor Proteins / Q000037:antagonists & inhibitors; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D051981:Uracil-DNA Glycosidase / Q000037:antagonists & inhibitors; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors; D000099224:p300-CBP-Associated Factor
D019380:Anti-HIV Agents; D018834:Chaperonin 60; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D019427:HIV Integrase; D019428:HIV Integrase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D063151:Polycomb Repressive Complex 2; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D000071796:SMARCB1 Protein; D014157:Transcription Factors; D051981:Uracil-DNA Glycosidase; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C491488:EED protein, human; C108381:GEMIN2 protein, human; C513266:SMARCB1 protein, human; C119380:lens epithelium-derived growth factor; C514801:p31 integrase protein, Human immunodeficiency virus 1