Integrase-LEDGF/p75 complex triggers the formation of biomolecular condensates that modulate HIV-1 integration efficiency in vitro

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The pre-integration steps of the HIV-1 viral cycle are some of the most valuable targets of recent therapeutic innovations. HIV-1 integrase (IN) displays multiple functions, thanks to its considerable conformational flexibility. Recently, such flexible proteins have been characterized by their ability to form biomolecular condensates as a result of Liquid-Liquid-Phase-Separation (LLPS), allowing them to evolve in a restricted microenvironment within cells called membrane less organelles (MLO). We investigated here if such complexes can form LLPS in vitro and if IN enzymatic activities were affected by this LLPS environment. In collaboration with M. Ruff”s team in IGBMC Strasbourg, we observed that LLPS can be induced by IN in complex with its cofactor LEDGF/p75 and can modulate the in vitro IN activities. Our data in combination with the increasing amount of observations reported in the literature point out a role of LLPS in the functional transit of integration complexes from the site of disassembly of the capsid and reverse transcription to the chromatin insertion regions through the membrane less organels formed by these bio condensates.