Foamy virus vector integration sites in normal human cells

GD Trobridge, DG Miller, MA Jacobs… - Proceedings of the …, 2006 - National Acad Sciences
GD Trobridge, DG Miller, MA Jacobs, JM Allen, HP Kiem, R Kaul, DW Russell
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
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 …
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.
National Acad Sciences