After retroviral infection of a target cell, during the early phase of replication, the HIV-1 genomic RNA is reverse transcribed by the viral RT to generate the double-stranded DNA that interact with viral and cellular proteins to form the pre-integration complex (PIC). Viral integrase (IN) is the key component of the PIC and is involved in several steps of replication notably in reverse transcription, nuclear import, chromatin targeting and integration. Viral components such as IN cannot perform these functions on their own and need to recruit host cell proteins to efficiently carry out the different processes. IN is a flexible protein, property allowing its interaction with multiple partners and enabling its multiple functions. To study the molecular mechanisms of viral integration we use a bottom-up strategy by assembling in vitro and/or in cellulo multiprotein complexes around the integrase protein (core protein of the PIC) and DNA. This strategy enabled us to solve cryo-EM structures of the IN/LEDGF and IN/LEDGF/INI1 complexes at low resolution [1, 2]. With the recent progress of the cryo-EM techniques and our improvement in the complex preparations [3] new cryo-EM datasets on the IN/LEDGF/DNA and IN/LEDGF/nucleosome complexes are collected which will enable us to increase the structure quality to near atomic resolution for the IN/LEDGF/DNA complex. Moreover, the efficient production of the proteins in mammalian cells allowed us to identify PTMs on HIV integrase. Their effect on viral replication and 3’processing are analyzed. The diverse structures and functions of HIV-1 integrase induced by protein and DNA interactions as well as by PTMs will be presented and discussed.[1] Michel et al.(2009) EMBO J., 28, 980-991.[2] Maillot et al.(2013) PLoS ONE 8 (4): e60734.[3] Levy et al.(2016) Nature comm. 7: 10932.