title: Hepatocyte growth factor receptor is a coreceptor for adeno-associated virus type 2 infection.
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 alphavbeta5 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 beta 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.
authors.affiliation: Department of Cardiology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kashiwakura
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamayose
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hirai
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimada
authors.forename: Kunio
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kazuo
authors.initials: K
authors.lastname: Oshimi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Daida
mesh_terms: D016475:3T3 Cells; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006367:HeLa Cells; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D051379:Mice; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D011991:Receptors, Virus; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met