LEDGINs and the molecular mechanism of LEDGF/p75 mediated HIV integration.

In 2002 we identified Lens Epithelium Derived Growth Factor (LEDGF/p75) as a novel cofactor of the integration and replication of the human immunodeficiency virus type 1 (HIV-1). We and others validated LEDGF/p75 as a crucial cofactor for targeting HIV integration into transcriptionally active regions. An artificial fusion of LEDGF/p75 to the heterochromatin binding protein CBX-1 does retarget HIV integration. Recently, we developed LEDGINs, small molecule inhibitors of the interaction between HIV-1 integrase and LEDGF/p75 that potently inhibit viral replication in cell culture. In this new project we will investigate whether treatment with LEDGINs retargets HIV integration by sequencing integration sites in infected cells. Next, we will explore whether LEDGIN or CBX1-LEDGF/p75 therapy can reduce HIV reactivation from latency as a potential strategy to cope with persistent HIV infection.

Keywords:HIV, LATENCY, COFACTORs, INTEGRATIO, LEDGIN, AIDS

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences