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 Brindley, M. A.
Right arrow Articles by Maury, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brindley, M. A.
Right arrow Articles by Maury, W.

 Previous Article  |  Next Article 

Journal of Virology, July 2007, p. 7702-7709, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.02433-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Ebola Virus Glycoprotein 1: Identification of Residues Important for Binding and Postbinding Events{triangledown}

Melinda A. Brindley,1 Laura Hughes,2 Autumn Ruiz,1,{dagger} Paul B. McCray Jr.,3 Anthony Sanchez,4 David A. Sanders,2 and Wendy Maury1*

Department of Microbiology,1 Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242,3 Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907,2 Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia4

Received 5 November 2006/ Accepted 20 April 2007

The filoviruses Ebola virus (EBOV) and Marburg virus (MARV) are responsible for devastating hemorrhagic fever outbreaks. No therapies are available against these viruses. An understanding of filoviral glycoprotein 1 (GP1) residues involved in entry events would facilitate the development of antivirals. Towards this end, we performed alanine scanning mutagenesis on selected residues in the amino terminus of GP1. Mutant GPs were evaluated for their incorporation onto feline immunodeficiency virus (FIV) particles, transduction efficiency, receptor binding, and ability to be cleaved by cathepsins L and B. FIV virions bearing 39 out of 63 mutant glycoproteins transduced cells efficiently, whereas virions bearing the other 24 had reduced levels of transduction. Virions pseudotyped with 23 of the poorly transducing GPs were characterized for their block in entry. Ten mutant GPs were very poorly incorporated onto viral particles. Nine additional mutant GPs (G87A/F88A, K114A/K115A, K140A, G143A, P146A/C147A, F153A/H154A, F159A, F160A, and Y162A) competed poorly with wild-type GP for binding to permissive cells. Four of these nine mutants (P146A/C147A, F153A/H154A, F159A, and F160A) were also inefficiently cleaved by cathepsins. An additional four mutant GPs (K84A, R134A, D150A, and E305/E306A) that were partially defective in transduction were found to compete effectively for receptor binding and were readily cleaved by cathepsins. This finding suggested that this latter group of mutants might be defective at a postbinding, cathepsin cleavage-independent step. In total, our study confirms the role of some GP1 residues in EBOV entry that had previously been recognized and identifies for the first time other residues that are important for productive entry.

* Corresponding author. Mailing address: 3-612 Bowen Science Bldg., Department of Microbiology, University of Iowa, Iowa City, IA 52242. Phone: (319) 335-8021. Fax: (319) 335-9006. E-mail: wendy-maury{at}uiowa.edu

{triangledown} Published ahead of print on 2 May 2007.

{dagger} Present address: University of Kansas Medical Center, Kansas City, KS 66160.

Journal of Virology, July 2007, p. 7702-7709, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.02433-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dube, D., Brecher, M. B., Delos, S. E., Rose, S. C., Park, E. W., Schornberg, K. L., Kuhn, J. H., White, J. M. (2009). The Primed Ebolavirus Glycoprotein (19-Kilodalton GP1,2): Sequence and Residues Critical for Host Cell Binding. J. Virol. 83: 2883-2891 [Abstract] [Full Text]  
  • Cote, M., Kucharski, T. J., Liu, S.-L. (2008). Enzootic Nasal Tumor Virus Envelope Requires a Very Acidic pH for Fusion Activation and Infection. J. Virol. 82: 9023-9034 [Abstract] [Full Text]  
  • Dube, D., Schornberg, K. L., Stantchev, T. S., Bonaparte, M. I., Delos, S. E., Bouton, A. H., Broder, C. C., White, J. M. (2008). Cell Adhesion Promotes Ebola Virus Envelope Glycoprotein-Mediated Binding and Infection. J. Virol. 82: 7238-7242 [Abstract] [Full Text]  
  • Brindley, M. A., Maury, W. (2008). Equine Infectious Anemia Virus Entry Occurs through Clathrin-Mediated Endocytosis. J. Virol. 82: 1628-1637 [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»