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 Kirschner, A. N.
Right arrow Articles by Jardetzky, T. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kirschner, A. N.
Right arrow Articles by Jardetzky, T. S.

 Previous Article  |  Next Article 

Journal of Virology, September 2007, p. 9216-9229, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00575-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Binding-Site Interactions between Epstein-Barr Virus Fusion Proteins gp42 and gH/gL Reveal a Peptide That Inhibits both Epithelial and B-Cell Membrane Fusion{triangledown}

Austin N. Kirschner,1,{dagger} Amanda S. Lowrey,2,{dagger} Richard Longnecker,2 and Theodore S. Jardetzky1*

Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208,1 Department of Microbiology and Immunology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 606112

Received 19 March 2007/ Accepted 11 June 2007

Herpesviruses require membrane-associated glycoproteins gB, gH, and gL for entry into host cells. Epstein-Barr virus (EBV) gp42 is a unique protein also required for viral entry into B cells. Key interactions between EBV gp42 and the EBV gH/gL complex were investigated to further elucidate their roles in membrane fusion. Deletion and point mutants within the N-terminal region of gp42 revealed residues important for gH/gL binding and membrane fusion. Many five-residue deletion mutants in the N-terminal region of gp42 that exhibit reduced membrane fusion activity retain binding with gH/gL but map out two functional stretches between residues 36 and 96. Synthetic peptides derived from the gp42 N-terminal region were studied in in vitro binding experiments with purified gH/gL and in cell-cell fusion assays. A peptide spanning gp42 residues 36 to 81 (peptide 36-81) binds gH/gL with nanomolar affinity, comparable to full-length gp42. Peptide 36-81 efficiently inhibits epithelial cell membrane fusion and competes with soluble gp42 to inhibit B-cell fusion. Additionally, this peptide at low nanomolar concentrations inhibits epithelial cell infection by intact virus. Shorter gp42 peptides spanning the two functional regions identified by deletion mutagenesis had little or no binding to soluble gH/gL and were also unable to inhibit epithelial cell fusion, nor could they complement gp42 deletion mutants in B-cell fusion. These studies identify key residues of gp42 that are essential for gH/gL binding and membrane fusion activation, providing a nanomolar inhibitor of EBV-mediated membrane fusion.

* Corresponding author. Mailing address: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208. Phone: (847) 467-4048. Fax: (847) 467-6489. E-mail: tedj{at}northwestern.edu

{triangledown} Published ahead of print on 20 June 2007.

{dagger} A.N.K. and A.S.L. contributed equally to this paper.

Journal of Virology, September 2007, p. 9216-9229, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00575-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sorem, J., Jardetzky, T. S., Longnecker, R. (2009). Cleavage and Secretion of Epstein-Barr Virus Glycoprotein 42 Promote Membrane Fusion with B Lymphocytes. J. Virol. 83: 6664-6672 [Abstract] [Full Text]  
  • Gianni, T., Amasio, M., Campadelli-Fiume, G. (2009). Herpes Simplex Virus gD Forms Distinct Complexes with Fusion Executors gB and gH/gL in Part through the C-terminal Profusion Domain. J. Biol. Chem. 284: 17370-17382 [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»