HIV-1 integrase–lens epithelium-derived growth factor interaction (HIV-1 IN–LEDGF/p75 interaction)

The HIV-1 integrase–lens epithelium-derived growth factor interaction refers to a critical protein–protein interaction where the HIV-1 integrase enzyme binds to the host protein LEDGF/p75 (also called PSIP1), specifically through the integrase-binding domain (IBD) at the C-terminus of LEDGF/p75 and the catalytic core of integrase[4][5][6]. This interaction tethers the HIV-1 pre-integration complex to active chromatin and directs integration of viral DNA into host genes, a key step in the viral replication cycle[1][3][7]. Disrupting this interaction impairs HIV-1 replication, making it a validated therapeutic target for antiretroviral development; small molecules termed LEDGINs have been designed to specifically inhibit this interface[6][7]. LEDGF/p75 also plays broader roles as a transcriptional coactivator and protective factor in cell survival and is implicated in MLL fusion-driven leukemias, raising considerations for therapeutic selectivity and safety[4][6].

Other names

HIV-1 integrase–LEDGF/p75 interactionHIV-1 IN–LEDGF interactionHIV-1 IN–PSIP1 interactionIntegrase–lens epithelium-derived growth factor interactionIntegrase–PSIP1 interaction

Inhibition of IN–LEDGF/p75 binding Disruption of integrase chromatin tethering, preventing efficient viral DNA integration Allosteric modulation of integrase function