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Journal of Virology, January 2005, p. 609-614, Vol. 79, No. 1
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.1.609-614.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Hepatocyte Growth Factor Receptor Is a Coreceptor for Adeno-Associated Virus Type 2 Infection

Yuji Kashiwakura,1 Kenji Tamayose,2* Kazuhisa Iwabuchi,3 Yukihiko Hirai,4 Takashi Shimada,4 Kunio Matsumoto,5 Toshikazu Nakamura,5 Masami Watanabe,6 Kazuo Oshimi,2 and Hiroyuki Daida1

Departments of Cardiology,1 Hematology, Juntendo University School of Medicine,2 Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo,4 Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba,3 Division of Molecular Regenerative Medicine, Course of Advanced Medicine, Osaka University Graduate School of Medicine, Osaka,5 Department of Urology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan6

Received 9 January 2004/ Accepted 1 July 2004

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 {alpha}vß5 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 ß 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.

* Corresponding author. Mailing address: Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Phone: 81-3-3813-3111, ext. 3386. Fax: +81-3-3813-0841. E-mail: tamayose{at}med.juntendo.ac.jp.

Journal of Virology, January 2005, p. 609-614, Vol. 79, No. 1
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.1.609-614.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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