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Interaction of penton base Arg-Gly-Asp motifs with integrins is crucial for adenovirus serotype 35 vector transduction in human hematopoietic cells

Gene Therapy volume 14, pages 1525–1533 (2007)Cite this article

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.

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Acknowledgements

We thank Ms Kimiyo Akitomo for her technical assistance. This work was supported by grants for Health and Labour Sciences Research from the Ministry of Health, Labour and Welfare of Japan.

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Author notes

  1. S Murakami and F Sakurai: These authors contributed equally to this work

Authors and Affiliations

  1. Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan

    S Murakami, F Sakurai, K Kawabata & H Mizuguchi

  2. Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto, Japan

    S Murakami, N Okada, T Fujita & A Yamamoto

  3. Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

    N Okada & H Mizuguchi

  4. Pharmaceuticals and Medical Devices Agency, Tokyo, Japan

    T Hayakawa

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  1. S Murakami
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Correspondence to H Mizuguchi.

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Murakami, S., Sakurai, F., Kawabata, K. et al. Interaction of penton base Arg-Gly-Asp motifs with integrins is crucial for adenovirus serotype 35 vector transduction in human hematopoietic cells. Gene Ther 14, 1525–1533 (2007). https://doi.org/10.1038/sj.gt.3303019

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