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Journal of Virology, December 2002, p. 12463-12472, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12463-12472.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Covalent Modifications of the Ebola Virus Glycoprotein

Scott A. Jeffers,1 David Avram Sanders,1* and Anthony Sanchez2

Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907,1 Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 303332

Received 8 July 2002/ Accepted 6 September 2002

The role of covalent modifications of the Ebola virus glycoprotein (GP) and the significance of the sequence identity between filovirus and avian retrovirus GPs were investigated through biochemical and functional analyses of mutant GPs. The expression and processing of mutant GPs with altered N-linked glycosylation, substitutions for conserved cysteine residues, or a deletion in the region of O-linked glycosylation were analyzed, and virus entry capacities were assayed through the use of pseudotyped retroviruses. Cys-53 was the only GP1 (~130 kDa) cysteine residue whose replacement resulted in the efficient secretion of GP1, and it is therefore proposed that it participates in the formation of the only disulfide bond linking GP1 to GP2 (~24 kDa). We propose a complete cystine bridge map for the filovirus GPs based upon our analysis of mutant Ebola virus GPs. The effect of replacement of the conserved cysteines in the membrane-spanning region of GP2 was found to depend on the nature of the substitution. Mutations in conserved N-linked glycosylation sites proved generally, with a few exceptions, innocuous. Deletion of the O-linked glycosylation region increased GP processing, incorporation into retrovirus particles, and viral transduction. Our data support a common evolutionary origin for the GPs of Ebola virus and avian retroviruses and have implications for gene transfer mediated by Ebola virus GP-pseudotyped retroviruses.

* Corresponding author. Mailing address: Department of Biological Sciences, 1392 Lilly Hall, Purdue University, West Lafayette, IN 47907. Phone: (765) 494-6453. Fax: (765) 496-1189. E-mail: retrovir{at}bragg.bio.purdue.edu.

Journal of Virology, December 2002, p. 12463-12472, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12463-12472.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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