Integrase, LEDGF/p75 and HIV replication

E. M. Poeschla

Research output: Contribution to journalReview article

92 Scopus citations

Abstract

HIV integrates a DNA copy of its genome into a host cell chromosome in each replication cycle. The essential DNA cleaving and joining chemistry of integration is known, but there is less understanding of the process as it occurs in a cell, where two complex and dynamic macromolecular entities are joined: the viral pre-integration complex and chromatin. Among implicated cellular factors, much recent attention has coalesced around LEDGF/p75, a nuclear protein that may act as a chromatin docking factor or receptor for lentiviral pre-integration complexes. LEDGF/p75 tethers HIV integrase to chromatin, protects it from degradation, and strongly influences the genome-wide pattern of HIV integration. Depleting the protein from cells and/or over-expressing its integrase-binding domain blocks viral replication. Current goals are to establish the underlying mechanisms and to determine whether this knowledge can be exploited for antiviral therapy or for targeting lentiviral vector integration in human gene therapy.

Original languageEnglish (US)
Pages (from-to)1403-1424
Number of pages22
JournalCellular and Molecular Life Sciences
Volume65
Issue number9
DOIs
StatePublished - May 2008

Keywords

  • AT Hook
  • Chromatin
  • HIV
  • HRP-2
  • Integrase
  • Integration
  • LEDGF/p75
  • Lentivirus
  • PWWP domain

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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