This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fleischli, C.
Right arrow Articles by Hemmi, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fleischli, C.
Right arrow Articles by Hemmi, S.

 Previous Article  |  Next Article 

Journal of Virology, August 2005, p. 10013-10022, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.10013-10022.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Distal Short Consensus Repeats 1 and 2 of the Membrane Cofactor Protein CD46 and Their Distance from the Cell Membrane Determine Productive Entry of Species B Adenovirus Serotype 35

Christoph Fleischli,1 Sandra Verhaagh,2 Menzo Havenga,2 Dominique Sirena,1 Walter Schaffner,1 Roberto Cattaneo,3 Urs F. Greber,4 and Silvio Hemmi1*

Institute of Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland,1 Crucell Holland BV, Archimedesweg 4, 2333 CN Leiden, The Netherlands,2 Molecular Medicine Program and Virology and Gene Therapy Track, Mayo Clinic College of Medicine, Rochester, Minnesota 55905,3 Institute of Zoology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland4

Received 23 February 2005/ Accepted 22 April 2005

The human regulator of complement activation membrane cofactor protein (CD46) has recently been identified as an attachment receptor for most species B adenoviruses (Ads), including Ad type 3 (Ad3), Ad11, and Ad35, as well as species D Ad37. To characterize the interaction between Ad35 and CD46, hybrid receptors composed of different CD46 short consensus repeat (SCR) domains fused to immunoglobulin-like domains of CD4 and a set of 36 CD46 mutants containing semiconservative changes of single amino acids within SCR domains I and II were tested in binding and in Ad35-mediated luciferase transduction assays. In addition, anti-CD46 antibodies and soluble polypeptides constituting various CD46 domains were used in binding inhibition studies. Our data indicate that (i) CD46 SCR I or SCR II alone confers low but significant Ad35 binding; (ii) the presence of SCR I and II is required for optimal binding and transgene expression; (iii) transduction efficiencies equivalent to that of full-length CD46 are obtained if SCR I and II are at an appropriate distance from the cell membrane; (iv) ablation of the N-glycan attached to SCR I has no influence on receptor function, whereas ablation of the SCR II N-glycan results in about a two- to threefold reduction of binding and transgene expression; (v) most putative Ad35 binding residues are located on the same solvent-exposed face of the SCR I or SCR II domain, which are twisted by about 90°; and (vi) the putative Ad35 binding sites partly overlap with the measles virus binding surface.

* Corresponding author. Mailing address: Institute of Molecular Biology Zürich, Winterthurerstr. 190, CH-8057 Zurich, Switzerland. Phone: 41 44 635 3120. Fax: 41 44 635 6811. E-mail: hemmi{at}molbio.unizh.ch.

Journal of Virology, August 2005, p. 10013-10022, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.10013-10022.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Persson, B. D., Muller, S., Reiter, D. M., Schmitt, B. B. T., Marttila, M., Sumowski, C. V., Schweizer, S., Scheu, U., Ochsenfeld, C., Arnberg, N., Stehle, T. (2009). An Arginine Switch in the Species B Adenovirus Knob Determines High-Affinity Engagement of Cellular Receptor CD46. J. Virol. 83: 673-686 [Abstract] [Full Text]  
  • Wang, H., Liu, Y., Li, Z., Tuve, S., Stone, D., Kalyushniy, O., Shayakhmetov, D., Verlinde, C. L. M., Stehle, T., McVey, J., Baker, A., Peng, K.-W., Roffler, S., Lieber, A. (2008). In Vitro and In Vivo Properties of Adenovirus Vectors with Increased Affinity to CD46. J. Virol. 82: 10567-10579 [Abstract] [Full Text]  
  • Pache, L., Venkataraman, S., Reddy, V. S., Nemerow, G. R. (2008). Structural Variations in Species B Adenovirus Fibers Impact CD46 Association. J. Virol. 82: 7923-7931 [Abstract] [Full Text]  
  • Wang, H., Liaw, Y.-C., Stone, D., Kalyuzhniy, O., Amiraslanov, I., Tuve, S., Verlinde, C. L. M. J., Shayakhmetov, D., Stehle, T., Roffler, S., Lieber, A. (2007). Identification of CD46 Binding Sites within the Adenovirus Serotype 35 Fiber Knob. J. Virol. 81: 12785-12792 [Abstract] [Full Text]  
  • Fleischli, C., Sirena, D., Lesage, G., Havenga, M. J. E., Cattaneo, R., Greber, U. F., Hemmi, S. (2007). Species B adenovirus serotypes 3, 7, 11 and 35 share similar binding sites on the membrane cofactor protein CD46 receptor. J. Gen. Virol. 88: 2925-2934 [Abstract] [Full Text]  
  • Tuve, S., Wang, H., Ware, C., Liu, Y., Gaggar, A., Bernt, K., Shayakhmetov, D., Li, Z., Strauss, R., Stone, D., Lieber, A. (2006). A New Group B Adenovirus Receptor Is Expressed at High Levels on Human Stem and Tumor Cells. J. Virol. 80: 12109-12120 [Abstract] [Full Text]  
  • Mathis, J. M., Stewart, P. L., Zhu, Z. B., Curiel, D. T. (2006). Advanced Generation Adenoviral Virotherapy Agents Embody Enhanced Potency Based upon CAR-Independent Tropism.. Clin. Cancer Res. 12: 2651-2656 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»