title: A new group B adenovirus receptor is expressed at high levels on human stem and tumor cells.
abstract: CD46 is used by human group B adenoviruses (Ads) as a high-affinity attachment receptor. Here we show evidence that several group B Ads utilize an additional receptor for infection of human cells, which is different from CD46. We tentatively named this receptor receptor X. Competition studies with unlabeled and labeled Ads, recombinant Ad fiber knobs, and soluble CD46 and CD46 antibodies revealed three different subgroups of group B Ads, in terms of their receptor usage. Group I (Ad16, -21, -35, and -50) nearly exclusively uses CD46. Group II (Ad3, -7p, and -14) utilizes receptor X and not CD46. Group III (Ad11p) uses both CD46 and the alternative receptor X. Interaction of group II and III Ads with receptor X occurs via the fiber knob. Receptor X is an abundantly expressed glycoprotein that interacts with group II and III Ads at relatively low affinity in a Ca(2+)-dependent manner. This receptor is expressed at high levels on human mesenchymal and undifferentiated embryonic stem cells, as well as on human cancer cell lines. These findings have practical implications for stem cell and gene therapy.
authors.affiliation: Division of Medical Genetics, Box 357720, University of Washington, Seattle, WA 98195, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Tuve
authors.forename: Hongjie
authors.initials: H
authors.lastname: Wang
authors.forename: Carol
authors.initials: C
authors.lastname: Ware
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Anuj
authors.initials: A
authors.lastname: Gaggar
authors.forename: Kathrin
authors.initials: K
authors.lastname: Bernt
authors.forename: Dmitry
authors.initials: D
authors.lastname: Shayakhmetov
authors.forename: Zongyi
authors.initials: Z
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Strauss
authors.forename: Daniel
authors.initials: D
authors.lastname: Stone
authors.forename: André
authors.initials: A
authors.lastname: Lieber
mesh_terms: D000260:Adenoviruses, Human / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000914:Antibodies, Viral / Q000378:metabolism; D045744:Cell Line, Tumor; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D051916:Membrane Cofactor Protein / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011991:Receptors, Virus / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D034741:RNA, Small Interfering; D011991:Receptors, Virus; D000469:Alkaline Phosphatase; D001616:beta-Galactosidase