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

Author:

Kashiwakura Yuji1,Tamayose Kenji2,Iwabuchi Kazuhisa3,Hirai Yukihiko4,Shimada Takashi4,Matsumoto Kunio5,Nakamura Toshikazu5,Watanabe Masami6,Oshimi Kazuo2,Daida Hiroyuki1

Affiliation:

1. Departments of Cardiology

2. Hematology, Juntendo University School of Medicine

3. Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba

4. Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo

5. Division of Molecular Regenerative Medicine, Course of Advanced Medicine, Osaka University Graduate School of Medicine, Osaka

6. Department of Urology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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