Cellular co-factors of HIV-1 integration.
To achieve productive infection, the reverse transcribed cDNA of human immunodeficiency virus type 1 (HIV-1) is inserted in the host cell genome. The main protein responsible for this reaction is the viral integrase. However, studies indicate that the virus is assisted by cellular proteins, or co-factors, to achieve integration into the infected cell. The barrier-to-autointegration factor (BAF) might prevent autointegration. Its ability to bridge DNA and the finding that the nuclear lamina-associated polypeptide-2alpha interacts with BAF suggest a role in nuclear structure organization. Integrase interactor 1 was found to directly interact with HIV-1 integrase and to activate its DNA-joining activity, and the high mobility group chromosomal protein A1 might approximate both long terminal repeat (LTR) ends and facilitate integrase binding by unwinding the LTR termini. Furthermore, the lens-epithelium-derived growth factor (LEDGF; also known as p75) seems to tether HIV-1 integrase to the chromosomes. Although a direct role in integration has only been demonstrated for LEDGF/p75, to date, each validated cellular co-factor for HIV-1 integration could constitute a promising new target for antiviral therapy.
Van Maele
Bénédicte
B
Molecular Virology and Gene Therapy, Molecular Medicine, KULAK and K.U. Leuven, Kapucijnenvoer 33 3000 Leuven, Flanders, Belgium.
Busschots
Katrien
K
Vandekerckhove
Linos
L
Christ
Frauke
F
Debyser
Zeger
Z
D000818:Animals; D002868:Chromosomal Proteins, Non-Histone; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D019427:HIV Integrase / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D025741:HMGA1a Protein / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000502:physiology; D016662:Virus Integration / Q000502:physiology*
C501959:BANF1 protein, human; D002868:Chromosomal Proteins, Non-Histone; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; C093413:lamina-associated polypeptide 2; C119380:lens epithelium-derived growth factor; D025741:HMGA1a Protein; D019427:HIV Integrase