Journal
TRENDS IN BIOCHEMICAL SCIENCES
Volume 40, Issue 2, Pages 108-116Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tibs.2014.12.001
Keywords
retrovirus; integration; integration site; LEDGF/p75; LEDGIN; BET proteins
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Funding
- Bijzonder Onderzoeksfonds (BOF) KU Leuven (OT-IDO)
- Belspo (BelVir)
- Fonds voor Wetenschappelijk Onderzoek (FWO)
- Agentschap voor Innovatie door Wetenschap en Technologie (IWT
- SBO program)
- European Commission
- ERAnet EURECA
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To achieve productive infection, retroviruses such as HIV stably integrate their reverse transcribed RNA genome into a host chromosome. Each retroviral family preferentially integrates near a unique subset of genomic features. HIV integrase (IN) is targeted to the body of active transcription units through interaction with lens epithelium-derived growth factor (LEDGF/p75). We describe the successful effort to develop inhibitors of the interaction between IN and LEDGF/p75, referred to as LEDGINs. Gammaretroviruses display a distinct integration pattern. Recently, BET (bromo- and extraterminal domain) proteins were identified as the LEDGF/p75 counterparts that target the integration of gammaretroviruses. The identification of the chromatin-readers LEDGF/p75 and BET as cellular cofactors that orchestrate lentiviral or gammaretrovirar integration opens new avenues to developing safer viral vectors for gene therapy.
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