Raghavendra Nidhanapati K, Engelman Alan
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Virology. 2007 Mar 30;360(1):1-5. doi: 10.1016/j.virol.2006.12.022. Epub 2007 Jan 26.
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.
整合酶二聚体在体外可处理并整合单个HIV-1 DNA末端,而整合两个末端则需要四聚体。LEDGF/p75可有效刺激整合酶活性,但其对半位点与全位点整合的影响尚未得到研究。本文揭示了其对半位点整合的刺激作用以及对全位点整合的抑制作用。LEDGF/p75似乎会干扰整合酶的寡聚化,但不抑制预组装复合物的催化活性。因此,我们推测LEDGF/p75的功能局限于病毒生命周期中在预整合突触复合物形成之后的某个阶段,例如作为一种与染色质相关的拴系因子。