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Host factors for retroviral integration site selection.

Authors
  • Debyser, Zeger1
  • Christ, Frauke2
  • De Rijck, Jan2
  • Gijsbers, Rik2
  • 1 Laboratory for Molecular Virology and Gene Therapy, KU Leuven, Leuven 3000, Flanders, Belgium. Electronic address: [email protected] , (Belgium)
  • 2 Laboratory for Molecular Virology and Gene Therapy, KU Leuven, Leuven 3000, Flanders, Belgium. , (Belgium)
Type
Published Article
Journal
Trends in Biochemical Sciences
Publisher
Elsevier
Publication Date
Feb 01, 2015
Volume
40
Issue
2
Pages
108–116
Identifiers
DOI: 10.1016/j.tibs.2014.12.001
PMID: 25555456
Source
Medline
Keywords
License
Unknown

Abstract

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 gammaretroviral integration opens new avenues to developing safer viral vectors for gene therapy.

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