A permanent cure remains the greatest challenge in the field of HIV research. In order to reach this goal, a profound understanding of the molecular mechanisms controlling HIV integration and transcription is needed. Here we provide an overview of recent advances in the field. Lens epithelium-derived growth factor p75 (LEDGF/p75), a transcriptional coactivator, tethers and targets the HIV integrase into transcriptionally active regions of the chromatin through an interaction with the epigenetic mark H3K36me2/3. This finding prompted us to propose a "block-and-lock" strategy to retarget HIV integration into deep latency. A decade ago, we pioneered protein-protein interaction inhibitors for HIV and discovered LEDGINs. LEDGINs are small molecule inhibitors of the interaction between the integrase binding domain (IBD) of LEDGF/p75 and HIV integrase. They modify integration site selection and therefore might be molecules with a "block-and-lock" mechanism of action. Here we will describe how LEDGINs may become part in the future functional cure strategies.
Keywords: HIV; Integrase; Integration site; LEDGF/p75; LEDGINs; Latency; Protein–protein interactions.
© 2021. The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.