Identification of PDGFR as a receptor for AAV-5 transduction

Pasquale, Giovanni Di; Davidson, Beverly L; Stein, Colleen S; Martins, Inês; Scudiero, Dominic; Monks, Anne; Chiorini, John A

doi:10.1038/nm929

Cited by 355Virus-based gene therapy researchRNA Interference and Gene DeliveryBarrier Structure and Function Studies

Identification of PDGFR as a receptor for AAV-5 transduction

Pasquale, Giovanni Di, Davidson, Beverly L, Stein, Colleen S, Martins, Inês, Scudiero, Dominic, Monks, Anne, Chiorini, John A·2003·Nature Medicine

DOI 10.1038/nm929

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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-alpha-polypeptide) and AAV-5 transduction. Subsequent experiments confirmed the role of PDGFR-alpha and PDGFR-beta as receptors for AAV-5. The tropism of AAV-5 in vivo also correlated with the expression pattern of PDGFR-alpha.

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The early steps of AAV infection involve attachment to a variety of cell surface receptors such as HSPG, FGFR, αvβ5 integrin, and hepatocyte growth factor receptor (c-Met), followed by clathrin-dependent endocytosis.
“The early steps of AAV infection involve attachment to a variety of cell surface receptors such as HSPG, FGFR, αvβ5 integrin, and hepatocyte growth factor receptor (c-Met) (Fig. 8I) (9, 25, 31, 39, 40), followed by clathrin-dependent endocytosis (Fig.8II).”
From Packaging Capacity of Adeno-Associated Virus Serotypes: Impact of Larger Genomes on Infectivity and Postentry Steps (2005) · cites this paper as [9]
The introduction lists HSPG, FGFR-1 and αvβ5 integrin among factors expressed by AAV-2-permissive cells, but does not identify c-Met as an AAV receptor. The Discussion also reports clathrin-coated-vesicle entry for AAV-5, rather than establishing that route for AAV generally. Page numbers are unavailable in our copy. (LLM, conf=0.86)
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Authors: Pasquale, G. D., Davidson, B. L., Stein, C. S., Martins, I., Scudiero, D., Monks, A., & Chiorini, J. A.
Affiliations: National Institutes of Health (US)
University of Iowa (US)
Science Applications International Corporation (United States) (US)
Corresponding author: Chiorini, John A
ORCID: Pasquale, Giovanni Di
Davidson, Beverly L
Stein, Colleen S
Chiorini, John A
Venue: Nature Medicine
Publisher: Springer Science and Business Media LLC
Published: 2003-09-14
Volume: 9
Issue: 10
Pages: 1306-1312
ISSN: 1078-8956 (ISSN-L)
1546-170X
DOI: 10.1038/nm929
OpenAlex: W2066015597
Cited by: 355
References: 2
Citations by year: 2026: 1 · 2025: 4 · 2024: 7 · 2023: 12 · 2022: 10 · 2021: 9 · 2020: 12 · 2019: 11 · 2018: 10 · 2017: 8 · 2016: 9 · 2015: 14 · 2014: 21 · 2013: 21 · 2012: 17
FWCI: 15.49
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: platelet-derived growth factor receptor, PDGFRA, PDGFRβ, viral tropism, gene therapy vectors, gene expression profiling
MeSH terms: Dependovirus, Animals, Cell Line, Genetic Vectors, Hippocampus, Humans, Statistics as Topic, Transduction, Genetic, Genetic Therapy, Receptors, Platelet-Derived Growth Factor, Protein Isoforms, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, ErbB Receptors

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Identification of PDGFR as a receptor for AAV-5 transduction

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