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 Silva, A. L.
Right arrow Articles by Longnecker, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Silva, A. L.
Right arrow Articles by Longnecker, R.

 Previous Article  |  Next Article 

Journal of Virology, June 2004, p. 5946-5956, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5946-5956.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mutational Analyses of Epstein-Barr Virus Glycoprotein 42 Reveal Functional Domains Not Involved in Receptor Binding but Required for Membrane Fusion

Amanda L. Silva,1 Jasmina Omerovi,1 Theodore S. Jardetzky,2 and Richard Longnecker1*

Department of Microbiology and Immunology, Northwestern University Medical School, Chicago, Illinois 60611,1 Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 602082

Received 30 October 2003/ Accepted 15 January 2004

Epstein-Barr virus (EBV) is a human gammaherpesvirus associated with malignancies of both epithelial and lymphoid origin. Efficient infection of the latent host reservoir B lymphocytes involves the binding of glycoproteins gp350/220 for initial attachment, followed by the concerted action of gH, gL, gB, and gp42 for membrane fusion. The type II membrane protein gp42 is required for infection of B cells and assembles into a complex with gH and gL. The cellular host receptor for gp42, class II human leukocyte antigen (HLA), has been structurally verified by crystallization analyses of gp42 bound to HLA-DR1. Interestingly, the crystal structure revealed a hydrophobic pocket consisting of many aromatic and aliphatic residues from the predicted C-type lectin domain of gp42 that in other members of the C-type lectin family binds major histocompatibility complex class I or other diverse ligands. Although the hydrophobic pocket does not bind HLA class II, mutational analyses presented here indicate that this domain is essential for EBV-induced membrane fusion. In addition, mutational analysis of the region of gp42 contacting HLA class II in the gp42-HLA-DR1 cocrystal confirms that this region interacts with HLA class II and that this interaction is also important for EBV-induced membrane fusion.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Northwestern University Medical School, Ward 6-231, Chicago, IL 60611. Phone: (312) 503-0467. Fax: (312) 503-1339. E-mail: r-longnecker{at}northwestern.edu.

Journal of Virology, June 2004, p. 5946-5956, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5946-5956.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Plate, A. E., Smajlovic, J., Jardetzky, T. S., Longnecker, R. (2009). Functional Analysis of Glycoprotein L (gL) from Rhesus Lymphocryptovirus in Epstein-Barr Virus-Mediated Cell Fusion Indicates a Direct Role of gL in gB-Induced Membrane Fusion. J. Virol. 83: 7678-7689 [Abstract] [Full Text]  
  • 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]  
  • Sorem, J., Longnecker, R. (2009). Cleavage of Epstein-Barr virus glycoprotein B is required for full function in cell-cell fusion with both epithelial and B cells. J. Gen. Virol. 90: 591-595 [Abstract] [Full Text]  
  • Reimer, J. J., Backovic, M., Deshpande, C. G., Jardetzky, T., Longnecker, R. (2009). Analysis of Epstein-Barr Virus Glycoprotein B Functional Domains via Linker Insertion Mutagenesis. J. Virol. 83: 734-747 [Abstract] [Full Text]  
  • Backovic, M., Jardetzky, T. S., Longnecker, R. (2007). Hydrophobic Residues That Form Putative Fusion Loops of Epstein-Barr Virus Glycoprotein B Are Critical for Fusion Activity. J. Virol. 81: 9596-9600 [Abstract] [Full Text]  
  • Kirschner, A. N., Lowrey, A. S., Longnecker, R., Jardetzky, T. S. (2007). 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. J. Virol. 81: 9216-9229 [Abstract] [Full Text]  
  • Hutt-Fletcher, L. M. (2007). Epstein-Barr Virus Entry. J. Virol. 81: 7825-7832 [Full Text]  
  • Kirschner, A. N., Omerovic, J., Popov, B., Longnecker, R., Jardetzky, T. S. (2006). Soluble Epstein-Barr Virus Glycoproteins gH, gL, and gp42 Form a 1:1:1 Stable Complex That Acts Like Soluble gp42 in B-Cell Fusion but Not in Epithelial Cell Fusion. J. Virol. 80: 9444-9454 [Abstract] [Full Text]  
  • Omerovic, J., Lev, L., Longnecker, R. (2005). The Amino Terminus of Epstein-Barr Virus Glycoprotein gH Is Important for Fusion with Epithelial and B Cells. J. Virol. 79: 12408-12415 [Abstract] [Full Text]  
  • Galdiero, S., Falanga, A., Vitiello, M., Browne, H., Pedone, C., Galdiero, M. (2005). Fusogenic Domains in Herpes Simplex Virus Type 1 Glycoprotein H. J. Biol. Chem. 280: 28632-28643 [Abstract] [Full Text]  
  • Ressing, M. E., van Leeuwen, D., Verreck, F. A. W., Keating, S., Gomez, R., Franken, K. L. M. C., Ottenhoff, T. H. M., Spriggs, M., Schumacher, T. N., Hutt-Fletcher, L. M., Rowe, M., Wiertz, E. J. H. J. (2005). Epstein-Barr Virus gp42 Is Posttranslationally Modified To Produce Soluble gp42 That Mediates HLA Class II Immune Evasion. J. Virol. 79: 841-852 [Abstract] [Full Text]  
  • McShane, M. P., Longnecker, R. (2004). Cell-surface expression of a mutated Epstein-Barr virus glycoprotein B allows fusion independent of other viral proteins. Proc. Natl. Acad. Sci. USA 101: 17474-17479 [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»