Abstract
BackgroundLentiviral 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.ResultsA 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.ConclusionThese findings identify a previously uncharacterized but consistent cellular response to viral components and provide a novel example of environmentally modified epigenome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-016-0077-1) contains supplementary material, which is available to authorized users.
Highlights
Lentiviral vectors (LV) are widely used for various gene transfer or gene therapy applications
We recently provided the first direct evidence that the in vitro transduction of hematopoietic stem and progenitor cells (HSC) with LVs induces DNA methylation of CpG nucleotides within 24 h after the first contact between the cells and vectors [8]
The epigenetic effects of LV have not been characterized in depth and it is not known if they are caused by the lentiviral provirus or by the viral components before integration of the viral genome
Summary
Lentiviral vectors (LV) are widely used for various gene transfer or gene therapy applications. The maintenance of a coordinated gene expression pattern is largely dependent on the chromatin organization in the cell nucleus. Epigenetic mechanisms such as DNA methylation play a key role in determining chromatin structure. These mechanisms represent an interface between environment and genome function [1]. Lentiviral vectors (LV) are convenient tools to achieve stable gene transfer in target cells for research, engineering or clinical applications such as gene therapy studies [2]. The epigenetic effects of LV have not been characterized in depth and it is not known if they are caused by the lentiviral provirus or by the viral components before integration of the viral genome
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