HIV-1 integration in the human genome favors active genes and local hotspots.

Paradigms and Technologies
Methods Development
Therapeutic Approaches

Abstract

A defining feature of HIV replication is integration of the proviral cDNA into human DNA. The selection of chromosomal targets for integration is crucial for efficient viral replication, but the mechanism is poorly understood. Here we describe mapping of 524 sites of HIV cDNA integration on the human genome sequence. Genes were found to be strongly favored as integration acceptor sites. Global analysis of cellular transcription indicated that active genes were preferential integration targets, particularly genes that were activated in cells after infection by HIV-1. Regional hotspots for integration were also found, including a 2.4 kb region containing 1% of sites. These data document unexpectedly strong biases in integration site selection and suggest how selective targeting promotes aggressive HIV replication.

Authors

Schröder, Astrid R W; Shinn, Paul; Chen, Huaming; Berry, Charles; Ecker, Joseph R; Bushman, Frederic;

Keywords

  • Base Sequence/ genetics
  • Cells, Cultured
  • Chromosome Mapping
  • Chromosomes, Human, Pair 11/ genetics
  • Clone Cells
  • DNA, Complementary/ genetics
  • DNA, Satellite/ genetics
  • DNA, Viral/ genetics
  • Endogenous Retroviruses/ genetics
  • Gene Expression Regulation, Viral/ genetics
  • Gene Targeting
  • Genes/ genetics
  • Genome, Human
  • HIV Infections/ genetics
  • HIV-1/ genetics
  • HIV-1/ metabolism
  • Humans
  • Transcription, Genetic/ genetics
  • Virus Integration/ genetics
  • Virus Replication/ genetics

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