LEDGF/p75 interferes with the formation of synaptic nucleoprotein complexes that catalyze full-site HIV-1 DNA integration in vitro: implications for the mechanism of viral cDNA integration.
An integrase dimer can process and integrate a single HIV-1 DNA end in vitro, whereas a tetramer is required to integrate two ends. LEDGF/p75 can potently stimulate integrase activity, but its effects on half- versus full-site integration have not been investigated. Stimulation of half-site but inhibition of full-site integration is revealed here. LEDGF/p75 seems to interfere with integrase oligomerization, but does not inhibit the catalytic activity of pre-assembled complexes. We therefore speculate that LEDGF/p75 function is restricted to a point in the viral lifecycle that occurs after the formation of the preintegration synaptic complex, for example, as a chromatin-associated tethering factor.
Raghavendra
Nidhanapati K
NK
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Engelman
Alan
A
D018076:DNA, Complementary / Q000502:physiology*; D004279:DNA, Viral / Q000502:physiology*; D019427:HIV Integrase / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D009698:Nucleoproteins / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism / Q000821:virology*; D014764:Viral Proteins / Q000502:physiology*; D016662:Virus Integration
D018076:DNA, Complementary; D004279:DNA, Viral; D036341:Intercellular Signaling Peptides and Proteins; D009698:Nucleoproteins; D014764:Viral Proteins; C119380:lens epithelium-derived growth factor; D019427:HIV Integrase