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 Sarrias, M. R.
Right arrow Articles by Lambris, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sarrias, M. R.
Right arrow Articles by Lambris, J. D.

 Previous Article  |  Next Article 

Journal of Virology, July 1999, p. 5681-5687, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Inhibition of Herpes Simplex Virus gD and Lymphotoxin-alpha Binding to HveA by Peptide Antagonists

Maria Rosa Sarrias,1 J. Charles Whitbeck,2,3 Isabelle Rooney,4 Lynn Spruce,1 Brian K. Kay,5 Rebecca I. Montgomery,6 Patricia G. Spear,6 Carl F. Ware,4 Roselyn J. Eisenberg,2 Gary H. Cohen,2,3 and John D. Lambris1,*

Laboratory of Protein Chemistry, Department of Pathology and Laboratory Medicine, School of Medicine,1 Department of Microbiology, School of Veterinary Medicine,2 and Center for Oral Health Research, School of Dental Medicine,3 University of Pennsylvania, Philadelphia, Pennsylvania 19104; Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 921214; Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 537065; and Department of Microbiology-Immunology, Northwestern Medical School, Chicago, Illinois 606116

Received 27 January 1999/Accepted 29 March 1999

The herpesvirus entry mediator A (HveA) is a recently characterized member of the tumor necrosis factor receptor family that mediates the entry of most herpes simplex virus type 1 (HSV-1) strains into mammalian cells. Studies on the interaction of HSV-1 with HveA have shown that of all the viral proteins involved in uptake, only gD has been shown to bind directly to HveA, and this binding mediates viral entry into cells. In addition to gD binding to HveA, the latter has been shown to interact with proteins of tumor necrosis factor receptor-associated factor family, lymphotoxin-alpha (LT-alpha ), and a membrane-associated protein referred to as LIGHT. To study the relationship between HveA, its natural ligands, and the viral proteins involved in HSV entry into cells, we have screened two phage-displayed combinatorial peptide libraries for peptide ligands of a recombinant form of HveA. Affinity selection experiments yielded two peptide ligands, BP-1 and BP-2, which could block the interaction between gD and HveA. Of the two peptides, only BP-2 inhibited HSV entry into CHO cells transfected with an HveA-expressing plasmid. When we analyzed these peptides for the ability to interfere with HveA binding to its natural ligand LT-alpha , we found that BP-1 inhibited the interaction of cellular LT-alpha with HveA. Thus, we have dissected the sites of interaction between the cell receptor, its natural ligand LT-alpha and gD, the virus-specific protein involved in HSV entry into cells.

* Corresponding author. Mailing address: Protein Chemistry Laboratory, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104-6079. Phone: (215) 662-6165. Fax: (215) 573-2059. E-mail: lambris{at}mail.med.upenn.edu.

Journal of Virology, July 1999, p. 5681-5687, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Cheung, T. C., Humphreys, I. R., Potter, K. G., Norris, P. S., Shumway, H. M., Tran, B. R., Patterson, G., Jean-Jacques, R., Yoon, M., Spear, P. G., Murphy, K. M., Lurain, N. S., Benedict, C. A., Ware, C. F. (2005). From The Cover: Evolutionarily divergent herpesviruses modulate T cell activation by targeting the herpesvirus entry mediator cosignaling pathway. Proc. Natl. Acad. Sci. USA 102: 13218-13223 [Abstract] [Full Text]  
  • Gonzalez, L. C., Loyet, K. M., Calemine-Fenaux, J., Chauhan, V., Wranik, B., Ouyang, W., Eaton, D. L. (2005). A coreceptor interaction between the CD28 and TNF receptor family members B and T lymphocyte attenuator and herpesvirus entry mediator. Proc. Natl. Acad. Sci. USA 102: 1116-1121 [Abstract] [Full Text]  
  • Koelle, D. M., Corey, L. (2003). Recent Progress in Herpes Simplex Virus Immunobiology and Vaccine Research. Clin. Microbiol. Rev. 16: 96-113 [Abstract] [Full Text]  
  • Connolly, S. A., Landsburg, D. J., Carfi, A., Wiley, D. C., Eisenberg, R. J., Cohen, G. H. (2002). Structure-Based Analysis of the Herpes Simplex Virus Glycoprotein D Binding Site Present on Herpesvirus Entry Mediator HveA (HVEM). J. Virol. 76: 10894-10904 [Abstract] [Full Text]  
  • Barton, E. S., Connolly, J. L., Forrest, J. C., Chappell, J. D., Dermody, T. S. (2001). Utilization of Sialic Acid as a Coreceptor Enhances Reovirus Attachment by Multistep Adhesion Strengthening. J. Biol. Chem. 276: 2200-2211 [Abstract] [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»