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Hepatocyte Growth Factor Receptor Is a Coreceptor for Adeno-Associated Virus Type 2 Infection
Open accessAbstract
After the first attachment of virus to the cell surface through a primary receptor, efficient entry of virus requires the presence of a coreceptor. For adeno-associated virus type 2 (AAV2) infection, heparan sulfate proteoglycan is supposed as the primary receptor, and αvβ5 integrin and FGFR1 are reported to act as coreceptors. In this study, we were able to demonstrate that hepatocyte growth factor receptor, c-Met, is also a coreceptor for AAV2 infection. AAV2-mediated transgene analyses revealed that c-Met expression significantly up-regulated transgene expression without increasing AAV2 cell binding. Moreover, a viral overlay assay elucidated the physical interaction between AAV2 and the β subunit of c-Met. These data suggest that c-Met plays the role of coreceptor for AAV2 infection by facilitating AAV2 internalization into the cytoplasm.
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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) (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 [25]
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“Similar to this, it has been discovered that AAV2 uses several cellular co-receptors in addition to FGFR1 and V5, including CD9 , laminin receptor (LamR) , hepatocyte growth factor receptor (HGFR), and 51 integrin [21-24], a putative integrin for AAV9 [25]; FGFR1 for AAV2 [16] and AAV3 [26]; platelet-derived growth fa…”
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“…and FPV (Park et al., 2005; Parker et al., 2001) and heparan sulfate, αvβ5 integrin, or growth factor receptors for adeno-associated viruses (AAV) (Kashiwakura et al., 2005; Summerford and Samulski, 1998; Summerford et al., 1999), even though sialic acid acts as a common attachment factor for…”
Olarewaju, O., Bentler, M., Breuer, J., Alioglu, F., Grabowski, A., Prosche, A., Sami, H., Ogris, M., & Büning, H. (2026) · Human Gene Therapy · doi:10.1177/10430342261465461
“12,17 After AAV2 ’ s attachment to HSPG, cell surface contact is stabilized through further interactions with hepatocyte growth factor receptor, 18 human fi broblast growth factor receptor 1, 19 or laminin receptor, 20 and binding to a (cid:1) b 5 or a 5 b 1 integrin induces vector uptake.”
HIV-1 hijacks HGF/c-MET signaling to promote viral entry and replication in primary CD4 + T cells
Tripathi, S., Allen, M. M., & Wu, L. J. (2026) · mBio · doi:10.1128/mbio.02090-26
“Furthermore, c-MET has also been reported to function as a coreceptor for adeno-associated virus 2 (AAV2) infection by facilitating viral internaliza tion into the cytoplasm (66).”
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Metadata
- Authors
- Kashiwakura, Y., Tamayose, K., Iwabuchi, K., Hirai, Y., Shimada, T., Matsumoto, K., Nakamura, T., Watanabe, M., Oshimi, K., & Daida, H.
- Affiliations
- Juntendo University (JP)
- Nippon Medical School (JP)
- The University of Osaka (JP)
- Okayama University (JP)
- Departments of Cardiology
- Corresponding author
- Tamayose, Kenji
- ORCID
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2005-01
- Volume
- 79
- Issue
- 1
- Pages
- 609-614
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC538679
- OpenAlex
- W2120683337
- Cited by
- 246
- References
- 37
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 11 · 2021: 16 · 2020: 10 · 2019: 12 · 2018: 8 · 2017: 13 · 2016: 9 · 2015: 15 · 2014: 8 · 2013: 13 · 2012: 12
- FWCI
- 8.92
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Keywords
- adeno-associated virus type 2, c-Met, co-receptors, viral entry, heparan sulfate proteoglycans, integrin αvβ5, FGFR1, transgene expression, viral internalization, receptor interaction
- MeSH terms
- Dependovirus, Animals, Cricetinae, HeLa Cells, Humans, Receptors, Virus, Transduction, Genetic, CHO Cells, 3T3 Cells, Hepatocyte Growth Factor, Proto-Oncogene Proteins c-met, Mice
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