title: HIV integration site distributions in resting and activated CD4+ T cells infected in culture.
abstract: OBJECTIVE
  The goal of this study was to investigate whether the location of HIV integration differs in resting versus activated T cells, a feature that could contribute to the formation of latent viral reservoirs via effects on integration targeting.
  
  
  METHODS
  Primary resting or activated CD4 T cells were infected with purified X4-tropic HIV in the presence and absence of nucleoside triphosphates and genomic locations of integrated provirus determined.
  
  
  METHODS
  We sequenced and analyzed a total of 2661 HIV integration sites using linker-mediated PCR and 454 sequencing. Integration site data sets were then compared to each other and to computationally generated random distributions.
  
  
  RESULTS
  HIV integration was favored in active transcription units in both cell types, but integration sites from activated cells were found more often in genomic regions that were dense in genes, dense in CpG islands, and enriched in G/C bases. Integration sites from activated cells were also more strongly correlated with histone methylation patterns associated with active genes.
  
  
  CONCLUSIONS
  These data indicate that integration site distributions show modest but significant differences between resting and activated CD4 T cells, and that integration in resting cells occurs more often in regions that may be suboptimal for proviral gene expression.
authors: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Troy
authors: T
authors: Brady
authors: Luis M
authors: LM
authors: Agosto
authors: Nirav
authors: N
authors: Malani
authors: Charles C
authors: CC
authors: Berry
authors: Una
authors: U
authors: O'Doherty
authors: Frederic
authors: F
authors: Bushman
mesh_terms: D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics; D016678:Genome; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016662:Virus Integration / Q000235:genetics*; D017735:Virus Latency
chemical_list: D004279:DNA, Viral