Systemic epigenetic response to recombinant lentiviral vectors independent of proviral integration

Arányi, Tamás and Stockholm, Daniel and Yao, Roseline and Poinsignon, Catherine and Wiart, Thibault and Paldi, András (2016) Systemic epigenetic response to recombinant lentiviral vectors independent of proviral integration. EPIGENETICS & CHROMATIN, 9 (1). p. 29. ISSN 1756-8935


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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. Conclusion: These findings identify a previously uncharacterized but consistent cellular response to viral components and provide a novel example of environmentally modified epigenome. © 2016 The Author(s).

Item Type: Article
Uncontrolled Keywords: virus particle; virus DNA cell DNA interaction; umbilical cord blood; priority journal; Lentivirinae; human cell; human; hematopoietic stem cell; gene cassette; epigenetics; DNA MODIFICATION; DNA methylation; CpG island; controlled study; cell transport; CD34 selection; ARTICLE; virus DNA; lentivirus vector; Cytosine; cell DNA; CD34 antigen
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
Depositing User: MTMT SWORD
Date Deposited: 08 Feb 2017 12:08
Last Modified: 08 Feb 2017 12:08

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