title: Human hepatocyte growth factor receptor is a cellular coreceptor for adeno-associated virus serotype 3.
abstract: Adeno-associated viruses (AAVs) use a variety of cellular receptors/coreceptors to gain entry into cells. A number of AAV serotypes are now available, and the cognate receptors/coreceptors for only a handful of those have been identified thus far. Of the 10 commonly used AAV serotypes, AAV3 is by far the least efficient in transducing cells in general. However, in our more recent studies, we observed that AAV3 vectors transduced human liver cancer cells remarkably well, which led to the hypothesis that AAV3 uses hepatocyte growth factor receptor (HGFR) as a cellular coreceptor for viral entry. AAV3 infection of human liver cancer cell lines was strongly inhibited by hepatocyte growth factor, HGFR-specific small interfering RNA, and anti-HGFR antibody, which corroborated this hypothesis. However, AAV3 vectors failed to transduce murine hepatocytes, both in vitro and in vivo, suggesting that AAV3 specifically uses human HGFR, but not murine HGFR, as a cellular coreceptor for transduction. AAV3 may prove to be a useful vector for targeting human liver cancers for the potential gene therapy.
authors.affiliation: Department of Pediatrics, University of Florida College of Medicine, Gainesville, 32611, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Ling
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.forename: Jasmine K
authors.initials: JK
authors.lastname: Kalsi
authors.forename: Giridhara R
authors.initials: GR
authors.lastname: Jayandharan
authors.forename: Baozheng
authors.initials: B
authors.lastname: Li
authors.forename: Wenqin
authors.initials: W
authors.lastname: Ma
authors.forename: Binbin
authors.initials: B
authors.lastname: Cheng
authors.forename: Samantha W Y
authors.initials: SW
authors.lastname: Gee
authors.forename: Katherine E
authors.initials: KE
authors.lastname: McGoogan
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Govindasamy
authors.forename: Li
authors.initials: L
authors.lastname: Zhong
authors.forename: Mavis
authors.initials: M
authors.lastname: Agbandje-McKenna
authors.forename: Arun
authors.initials: A
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D045744:Cell Line, Tumor; D000229:Dependovirus / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017434:Protein Structure, Tertiary; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D056189:Viral Tropism; D053586:Virus Internalization
chemical_list: D017978:Receptors, Growth Factor; D011991:Receptors, Virus; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met