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- Title
Interaction of penton base Arg-Gly-Asp motifs with integrins is crucial for adenovirus serotype 35 vector transduction in human hematopoietic cells.
- Authors
Murakami, S.; Sakurai, F.; Kawabata, K.; Okada, N.; Fujita, T.; Yamamoto, A.; Hayakawa, T.; Mizuguchi, H.
- Abstract
Most subgroup B adenoviruses (Ads), including adenovirus (Ad) serotype 35 (Ad35), bind to human CD46 as a receptor; however, the infection processes of subgroup B Ads following attachment to CD46 remain to be elucidated. Subgroup B Ads possess Arg-Gly-Asp (RGD) motifs in the penton base, similarly to subgroup C Ad serotypes 2 and 5. In this study, we examined the role of penton base RGD motifs in Ad35 vector-mediated transduction in human hematopoietic cells. Inhibition of interaction between integrins and the RGD motifs by divalent cation chelation and a synthetic RGD peptide reduced the transduction efficiencies of Ad35 vectors; however, the amounts of cell-associated vector DNA of Ad35 vectors at 4 or 37 °C were not decreased by divalent cation chelation or the RGD peptide. Mutation of penton base RGD motifs reduced the transduction efficiencies of Ad35 vectors, although the amounts of cell-associated vector DNA of Ad35 vectors at 4 or 37 °C were not altered by mutation of penton base RGD motifs in Ad35 vectors. Furthermore, preincubation with several types of anti-integrin antibodies significantly inhibited Ad35 vector-mediated transduction. These results suggest that interaction between integrins and penton base RGD motifs plays a crucial role in Ad35 vector-mediated transduction in hematopoietic cells, probably in the post-internalization steps.Gene Therapy (2007) 14, 1525–1533; doi:10.1038/sj.gt.3303019; published online 6 September 2007
- Subjects
INTEGRINS; ADENOVIRUSES; GENETIC transduction; HEMATOPOIETIC system; CHELATION therapy; GENE therapy
- Publication
Gene Therapy, 2007, Vol 14, Issue 21, p1525
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3303019