A new group B adenovirus receptor is expressed at high levels on human stem and tumor cells.
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.
Tuve
Sebastian
S
Division of Medical Genetics, Box 357720, University of Washington, Seattle, WA 98195, USA.
Wang
Hongjie
H
Ware
Carol
C
Liu
Ying
Y
Gaggar
Anuj
A
Bernt
Kathrin
K
Shayakhmetov
Dmitry
D
Li
Zongyi
Z
Strauss
Robert
R
Stone
Daniel
D
Lieber
André
A
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
D000914:Antibodies, Viral; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D034741:RNA, Small Interfering; D011991:Receptors, Virus; D000469:Alkaline Phosphatase; D001616:beta-Galactosidase