Chromatin tethering and retroviral integration: Recent discoveries and parallels with DNA viruses

Anne M. Meehan, Eric M. Poeschla

Research output: Contribution to journalReview article

17 Scopus citations

Abstract

Permanent integration of the viral genome into a host chromosome is an essential step in the life cycles of lentiviruses and other retroviruses. By archiving the viral genetic information in the genome of the host target cell and its progeny, integrated proviruses prevent curative therapy of HIV-1 and make the development of antiretroviral drug resistance irreversible. Although the integration reaction is known to be catalyzed by the viral integrase (IN), the manner in which retroviruses engage and attach to the chromatin target is only now becoming clear. Lens epithelium-derived growth factor (LEDGF/p75) is a ubiquitously expressed nuclear protein that binds to lentiviral IN protein dimers at its carboxyl terminus and to host chromatin at its amino terminus. LEDGF/p75 thus tethers ectopically expressed IN to chromatin. It also protects IN from proteosomal degradation and can stimulate IN catalysis in vitro. HIV-1 infection is inhibited at the integration step in LEDGF/p75-deficient cells, and the characteristic lentiviral preference for integration into active genes is also reduced. A model in which LEDGF/p75 acts to tether the viral preintegration complex to chromatin has emerged. Intriguingly, similar chromatin tethering mechanisms have been described for other retroelements and for large DNA viruses. Here we review the evidence supporting the LEDGF/p75 tethering model and consider parallels with these other viruses.

Original languageEnglish (US)
Pages (from-to)182-191
Number of pages10
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1799
Issue number3-4
DOIs
StatePublished - Mar 1 2010

    Fingerprint

Keywords

  • Chromatin
  • HIV-1
  • Herpesvirus
  • KSHV
  • LEDGF/p75
  • Lentivirus
  • Tether

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this