title: Systemic epigenetic response to recombinant lentiviral vectors independent of proviral integration.
abstract: BACKGROUND
  Lentiviral vectors (LV) are widely used for various gene transfer or gene therapy applications. The effects of LV on target cells are expected to be limited to gene delivery. Yet, human hematopoietic CD34+ cells respond to functional LVs as well as several types of non-integrating LVs by genome-wide DNA methylation changes.
  
  
  RESULTS
  A new algorithm for the analysis of 450K Illumina data showed that these changes were marked by de novo methylation. The same 4126 cytosines located in islands corresponding to 1059 genes were systematically methylated. This effect required cellular entry of the viral particle in the cells but not the genomic integration of the vector cassette. Some LV preparations induced only mild sporadic changes while others had strong effects suggesting that LV batch heterogeneity may be related to the extent of the epigenetic response.
  
  
  CONCLUSIONS
  These findings identify a previously uncharacterized but consistent cellular response to viral components and provide a novel example of environmentally modified epigenome.
authors.affiliation: Université Evry Val d'Essonne, UMRS_951, Genethon, 91002 Evry, France.
authors.forename: Tamas
authors.initials: T
authors.lastname: Aranyi
authors.affiliation: Ecole Pratique des Hautes Etudes, PSL Research University, UMRS_951, Genethon, 1 bis rue de l'Internationale, 91002 Evry, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stockholm
authors.affiliation: Genethon, 91002 Evry, France.
authors.forename: Roseline
authors.initials: R
authors.lastname: Yao
authors.affiliation: Université Evry Val d'Essonne, UMRS_951, Genethon, 91002 Evry, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Poinsignon
authors.affiliation: Genethon, 91002 Evry, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Wiart
authors.affiliation: Genethon, 91002 Evry, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Corre
authors.affiliation: Centre National de Génotypage, CEA-Institut de Génomique, 2, rue Gaston Crémieux, 91000 Evry, France.
authors.forename: Nizar
authors.initials: N
authors.lastname: Touleimat
authors.affiliation: Centre National de Génotypage, CEA-Institut de Génomique, 2, rue Gaston Crémieux, 91000 Evry, France.
authors.forename: Jörg
authors.initials: J
authors.lastname: Tost
authors.affiliation: Inserm, U951, Genethon, 1 bis rue de l'Internationale, 91002 Evry, France.|Genethon, 91002 Evry, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Galy
authors.affiliation: Ecole Pratique des Hautes Etudes, PSL Research University, UMRS_951, Genethon, 1 bis rue de l'Internationale, 91002 Evry, France.
authors.forename: Andràs
authors.identifier: 0000-0003-4446-7625
authors.initials: A
authors.lastname: Paldi