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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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Cites
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Identification of the Hepatocyte Growth Factor Receptor As the c- met Proto-Oncogene Product
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αVβ5 integrin: a co-receptor for adeno-associated virus type 2 infection
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Emerging Multipotent Aspects of Hepatocyte Growth Factor
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Self-citationInfectious entry pathway of adeno-associated virus and adeno-associated virus vectors
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“by on January 25, 2010 jvi.asm.org Downloaded from ( 2 ).”
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Adeno-Associated Virus (AAV) as a Vector for Gene Therapy
Naso, M. F., Tomkowicz, B., Perry, W. L., & Strohl, W. R. (2017) · BioDrugs · doi:10.1007/s40259-017-0234-5 · Cited by 1,362
Gene therapy using adeno-associated virus vectors
Daya, S., & Berns, K. I. (2008) · Clinical Microbiology Reviews · doi:10.1128/cmr.00008-08 · Cited by 926
“Internalization is enhanced by interactions with one or more of at least six known coreceptors including V5 integrins (63), fibroblast growth factor receptor 1 (53), hepatocyte growth factor receptor ( 35 ), v1 integrin (7), and laminin receptor (3).”
BackgroundAdeno-associated Virus Serotypes: Vector Toolkit for Human Gene Therapy
Wu, Z., Asokan, A., & Samulski, R. J. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.05.009 · Cited by 957
“Subsequent interactions with human fibroblast growth factor receptor 1 (FGFR1) [73], hepatocyte growth factor receptor [74], and integrins aVh5/a5h1 ([75], A.”
BackgroundZhong, L., Li, B., Mah, C. S., Govindasamy, L., Agbandje-McKenna, M., Cooper, M., Herzog, R. W., Zolotukhin, I., Warrington, K. H., Weigel-Van Aken, K. A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802866105 · Cited by 558
An essential receptor for adeno-associated virus infection
Pillay, S., Meyer, N. L., Puschnik, A. S., Davulcu, O., Diep, J., Ishikawa, Y., Jae, L. T., Wosen, J. E., Nagamine, C. M., Chapman, M. S., et al. (2016) · Nature · doi:10.1038/nature16465 · Cited by 532
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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