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Identification of PDGFR as a receptor for AAV-5 transduction

Nature Medicine volume 9, pages 1306–1312 (2003)Cite this article

Abstract

Understanding the process of vector transduction has important implications for the application and optimal use of a vector system for human gene therapy. Recent studies with vectors based on adeno-associated virus type 5 (AAV-5) have shown utility of this vector system in the lung, central nervous system, muscle and eye. To understand the natural tropism of this virus and to identify proteins necessary for AAV-5 transduction, we characterized 43 cell lines as permissive or nonpermissive for AAV-5 transduction and compared the gene expression profiles derived from cDNA microarray analyses of those cell lines. A statistically significant correlation was observed between expression of the platelet-derived growth factor receptor (PDGFR-α-polypeptide) and AAV-5 transduction. Subsequent experiments confirmed the role of PDGFR-α and PDGFR-β as receptors for AAV-5. The tropism of AAV-5 in vivo also correlated with the expression pattern of PDGFR-α.

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Figure 1: AAV-5 transduction profile and microarray-derived gene expression profiles for PDGFR-α and PDGFR-β.
Figure 2: SB203580 treatment of NCI60 cell lines HS578T, SNB19 and SF295, all of which are permissive for AAV-5 transduction.
Figure 3: AAV-5 transduction of HeLa and 32D cells expressing PDGFR-α, PDGFR-β or EGFR.
Figure 4: Ligand inhibition of AAV-5 binding and transduction.
Figure 5: AAV and PDGFR-α coprecipitation.
Figure 6: AAV-5 transduces PDGFR-α-expressing cells in the hippocampus.

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Acknowledgements

We thank B. Handelman for excellent technical assistance; S. Pillemer for help with statistical analysis; S. Leppla and B. Baum for discussion; S. Holbeck for help with the microarray analysis; and N. Lokker, M. Alimandi, G. Sherlock, A. Su, C. Lengel, C.H. Heldin and members of the Davidson laboratory for providing crucial reagents and discussion.

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Authors and Affiliations

  1. Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Giovanni Di Pasquale & John A Chiorini

  2. Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, 52242, Iowa, USA

    Beverly L Davidson, Colleen S Stein & Inês Martins

  3. Department of Neurology, University of Iowa College of Medicine, Iowa City, 52242, Iowa, USA

    Beverly L Davidson

  4. Department of Physiology & Biophysics, University of Iowa College of Medicine, Iowa City, 52242, Iowa, USA

    Beverly L Davidson

  5. SAIC-Frederick, Frederick, 21702, Maryland, USA

    Dominic Scudiero & Anne Monks

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  1. Giovanni Di Pasquale
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Correspondence to John A Chiorini.

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Pasquale, G., Davidson, B., Stein, C. et al. Identification of PDGFR as a receptor for AAV-5 transduction. Nat Med 9, 1306–1312 (2003). https://doi.org/10.1038/nm929

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