HIV-1 Integrase Forms Stable Tetramers and Associates with LEDGF/p75 Protein in Human Cells*

By P. Cherepanov, G. Maertens, P. Proost, B. Devreese, J. V. Van Beeumen, Y. Engelborghs, E. De Clercq, Z. Debyser. Journal of Biological Chemistry, 2003

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We studied human immunodeficiency virus, type 1 (HIV-1) integrase (IN) complexes derived from nuclei of human cells stably expressing the viral protein from a synthetic gene. We show that in the nuclear extracts IN exists as part of a large distinct complex with an apparent Stokes radius of 61 Å, which dissociates upon dilution yielding a core molecule of 41 Å. We isolated the IN complexes from cells expressing FLAG-tagged IN and demonstrated that the 41 Å core is a tetramer of IN, whereas 61 Å molecules are composed of IN tetramers associated with a cellular protein with an apparent molecular mass of 76 kDa. This novel integrase interacting protein was found to be identical to lens epithelium-derived growth factor (LEDGF/p75), a protein implicated in regulation of gene expression and cellular stress response. HIV-1 IN and LEDGF co-localized in the nuclei of human cells stably expressing IN. Furthermore, recombinant LEDGF robustly enhanced strand transfer activity of HIV-1 IN in vitro. Our findings indicate that the minimal IN molecule in human cells is a homotetramer, suggesting that at least an octamer of IN is required to accomplish coordinated integration of both retroviral long terminal repeats and that LEDGF is a cellular factor involved in this process.

Subfields: Infectious Diseases, Molecular Biology, Virology

View Paper: https://www.semanticscholar.org/paper/aa93b2e7e1810b95dd7d84e90d3cd43e7a485028

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