HIV-1 integration site preferences in pluripotent cells
Janet L Markman1, Robert M Silvers, Abibatou M N Ndoye
1Division of Infectious Diseases-Center for Human Virology, Thomas Jefferson University, Philadelphia, PA, USA.
Frontiers in Bioscience (Elite Edition)
|January 4, 2011
Summary
Human immunodeficiency virus type 1 (HIV-1)-based vectors show unique integration preferences in pluripotent stem cells, with 30% targeting telomeric regions, unlike somatic cells. This suggests specific cellular factors in pluripotent cells influence vector integration.
Area of Science:
- Gene Therapy
- Stem Cell Biology
- Molecular Virology
Background:
- Human immunodeficiency virus type 1 (HIV-1)-based vectors are crucial tools in gene therapy, primarily integrating into genes within somatic cells.
- Previous studies indicate no specific integration preferences in large chromosomal regions for these vectors in somatic cells.
- The advent of induced pluripotent stem (iPS) cells and their similarity to embryonic stem (ES) cells necessitates understanding vector integration in these unique cell types.
Purpose of the Study:
- To investigate the integration site preferences of HIV-1-based vectors within a pluripotent, embryonic stem (ES)-like cell line.
- To compare integration patterns in pluripotent cells with those observed in various somatic cells.
Main Methods:
- Utilized HIV-1-based vectors for integration studies in a pluripotent, ES-like cell line.
- Analyzed integration site locations using genomic analysis techniques.
- Compared obtained integration data with previously reported data from somatic cell studies.
Main Results:
- Approximately 30% of HIV-1-based vector integrations occurred in proximity to telomeres in the studied pluripotent cell line.
- This telomeric integration pattern was found to be unique to the pluripotent cell line when compared to various somatic cells.
- No distinct integration site preferences were previously observed in large chromosomal regions of somatic cells.
Conclusions:
- Pluripotent stem cells exhibit distinct HIV-1-based vector integration preferences, notably a significant targeting of telomeric regions.
- The observed unique integration pattern suggests the presence of specific cellular cofactors in pluripotent cells that mediate integration targeting.
- These putative cofactors are likely absent or less active in somatic cells, leading to different integration site selection.
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