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Journal of Virology, December 2006, p. 12109-12120, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01370-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A New Group B Adenovirus Receptor Is Expressed at High Levels on Human Stem and Tumor Cells{triangledown}

Sebastian Tuve,1 Hongjie Wang,1 Carol Ware,2 Ying Liu,1 Anuj Gaggar,3 Kathrin Bernt,4 Dmitry Shayakhmetov,1 ZongYi Li,1 Robert Strauss,1 Daniel Stone,1 and André Lieber1,3*

Division of Medical Genetics, Department of Medicine,1 Department of Comparative Medicine,2 Department of Pathology, University of Washington, Seattle, Washington 98195,3 Baylor College of Medicine, Houston, Texas 770304

Received 28 June 2006/ Accepted 26 September 2006

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 Ca2+-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.

* Corresponding author. Mailing address: Division of Medical Genetics, Box 357720, University of Washington, Seattle, WA 98195. Phone: (206) 221-3973. Fax: (206) 685-8675. E-mail: lieber00{at}u.washington.edu.

{triangledown} Published ahead of print on 4 October 2006.

Journal of Virology, December 2006, p. 12109-12120, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01370-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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