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Cited by 443Virus-based gene therapy researchRNA Interference and Gene DeliveryFibroblast Growth Factor Research

Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2

Qing, Keyun, Mah, Cathryn, Hansen, Jonathan, Zhou, Shangzhen, Dwarki, Varavani, Srivastava, Arun·1999·Nature Medicine
DOI 10.1038/4758
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Abstract

Adeno-associated virus 2 (AAV)-based vectors have gained attention as a potentially useful alternative to the more commonly used retroviral and adenoviral vectors for human gene therapy. Although AAV uses the ubiquitously expressed cell surface heparan sulfate proteoglycan (HSPG) as a receptor, the transduction efficiency of AAV vectors varies greatly in different cells and tissues in vitro and in vivo. We demonstrate here that cell surface expression of HSPG alone is insufficient for AAV infection, and that AAV also requires human fibroblast growth factor receptor 1 (FGFR1) as a co-receptor for successful viral entry into the host cell. We document that cells that do not express either HSPG or FGFR1 fail to bind AAV and, consequently, are resistant to infection by AAV. These non-permissive cells are successfully transduced by AAV vectors after stable transfections with cDNAs encoding the murine HSPG and the human FGFR1. Furthermore, AAV infection of permissive cells, known to express both FGFR1 and the epidermal growth factor receptor, is abrogated by treatment of cells with basic fibroblast growth factor, but not with epidermal growth factor. The identification of FGFR1 as a co-receptor for AAV should provide new insights not only into its role in the life cycle of AAV, but also in the optimal use of AAV vectors in human gene therapy.

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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 [31]

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Authors
Qing, K., Mah, C., Hansen, J., Zhou, S., Dwarki, V., & Srivastava, A.
Affiliations
Indiana University Indianapolis (US)
Corresponding author
Srivastava, Arun
ORCID
Srivastava, Arun
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
1999-01
Volume
5
Issue
1
Pages
71-77
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/4758
OpenAlex
W4206826545
Cited by
443
References
1
Citations by year
2026: 4 · 2025: 9 · 2024: 11 · 2023: 14 · 2022: 15 · 2021: 15 · 2020: 19 · 2019: 9 · 2018: 11 · 2017: 13 · 2016: 9 · 2015: 15 · 2014: 7 · 2013: 10 · 2012: 17
FWCI
16.72
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hl048342-03)
  • National Heart, Lung, and Blood Institute (HL-58881, HL-48342, HL-53586, P01HL053586, R01HL058881)
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Keywords
adeno-associated virus type 2, FGFR1, co-receptors, viral entry, heparan sulfate proteoglycans, adeno-associated virus vectors, gene therapy vectors, basic fibroblast growth factor, epidermal growth factor receptor, viral transduction efficiency
MeSH terms
Dependovirus, Animals, DNA-Binding Proteins, Fibroblast Growth Factors, HeLa Cells, Humans, Phosphorylation, Receptors, Virus, Ribonucleoproteins, Tumor Cells, Cultured, 3T3 Cells, Receptors, Fibroblast Growth Factor, Transgenes, Heparan Sulfate Proteoglycans, Receptor Protein-Tyrosine Kinases, Mice, Receptor, Fibroblast Growth Factor, Type 1

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