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 = 1,821) 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.
Trobridge
Grant D
GD
Department of Medicine, Division of Hematology, University of Washington, Seattle, WA 98195, USA.
Miller
Daniel G
DG
Jacobs
Michael A
MA
Allen
James M
JM
Kiem
Hans-Peter
HP
Kaul
Rajinder
R
Russell
David W
DW
D018952:Antigens, CD34 / Q000096:biosynthesis / Q000378:metabolism; D002460:Cell Line; D018899:CpG Islands; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000378:metabolism; D016678:Genome; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D016296:Mutagenesis; D020411:Oligonucleotide Array Sequence Analysis; D011533:Proviruses / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D016092:Spumavirus / Q000235:genetics*; D014158:Transcription, Genetic; D016662:Virus Integration
D018952:Antigens, CD34; D049452:Green Fluorescent Proteins; D004247:DNA