Foamy Virus Vector Integration Sites in Normal Human Cells

Foamy viruses (FVs) or spumaviruses are retroviruses that have been developed as vectors, but their integration patterns have not been described. We have performed a large-scale analysis of FV integration sites in unselected human fibroblasts (n = 1,008) and human CD34⁺ hematopoietic cells (n = 1,82...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 5; pp. 1498 - 1503
Main Authors:	Trobridge, Grant D., Miller, Daniel G., Jacobs, Michael A., Allen, James M., Kiem, Hans-Peter, Kaul, Rajinder, Russell, David W.
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 31-01-2006 National Acad Sciences
Subjects:	Antigens, CD34 - biosynthesis Antigens, CD34 - metabolism Biological Sciences Cell Line Cell lines Cellular biology CpG Islands DNA DNA - metabolism Fibroblasts Fibroblasts - metabolism Foamy virus Gene Expression Regulation Gene therapy Genes Genetic Therapy - methods Genetic vectors Genetic Vectors - metabolism Genome Genomes Green Fluorescent Proteins - metabolism Hematopoietic Stem Cells - cytology HIV Humans Medical research Models, Genetic Models, Statistical Mutagenesis Mutation Oligonucleotide Array Sequence Analysis Plasmids Proviruses Proviruses - genetics Retroviridae - genetics Retrovirus Spumavirus - genetics Stem cells Transcription, Genetic Virus Integration Viruses
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Summary:	Foamy viruses (FVs) or spumaviruses are retroviruses that have been developed as vectors, but their integration patterns have not been described. We have performed a large-scale analysis of FV integration sites in unselected human fibroblasts (n = 1,008) and human CD34⁺ hematopoietic cells (n = 1,821) by using a bacterial shuttle vector and a comparable analysis of lentiviral vector integration sites in CD34⁺ cells (n = 1,331). FV vectors had a distinct integration profile relative to other types of retroviruses. They did not integrate preferentially within genes, despite a modest preference for integration near transcription start sites and a significant preference for CpG islands. The genomewide distribution of FV vector proviruses was nonrandom, with both clusters and gaps. Transcriptional profiling showed that gene expression had little influence on integration site selection. Our findings suggest that FV vectors may have desirable integration properties for gene therapy applications.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Abbreviations: FV, foamy virus; MLV, murine leukemia virus; ASV, avian sarcoma virus; AAV, adeno-associated virus; PGK, phosphoglycerate kinase; RefSeq, Reference Sequence. Conflict of interest statement: No conflicts declared. This paper was submitted directly (Track II) to the PNAS office. Author contributions: G.D.T., D.G.M., H.-P.K., R.K., and D.W.R. designed research; G.D.T., D.G.M., M.A.J., and J.M.A. performed research; G.D.T., D.G.M., M.A.J., H.-P.K., and D.W.R. analyzed data; and G.D.T. and D.W.R. wrote the paper. Edited by Inder M. Verma, The Salk Institute for Biological Studies, La Jolla, CA, and approved December 5, 2005 To whom correspondence should be addressed. E-mail: drussell@u.washington.edu.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.0510046103