Ebola Virus and Avian Retroviruses Have Common Evolutionary Origin

[sharon sanders]

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,<SUP>1</SUP> David Avram Sanders,<SUP>1</SUP><SUP>*</SUP> and Anthony Sanchez<SUP>2</SUP>
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907,<SUP>1</SUP> Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333<SUP>2</SUP>
Received 8 July 2002/ Accepted 6 September 2002
<!-- ABS -->The role of covalent modifications of the Ebola virus glycoprotein<SUP> </SUP>(GP) and the significance of the sequence identity between filovirus<SUP> </SUP>and avian retrovirus GPs were investigated through biochemical<SUP> </SUP>and functional analyses of mutant GPs. The expression and processing<SUP> </SUP>of mutant GPs with altered N-linked glycosylation, substitutions<SUP> </SUP>for conserved cysteine residues, or a deletion in the region<SUP> </SUP>of O-linked glycosylation were analyzed, and virus entry capacities<SUP> </SUP>were assayed through the use of pseudotyped retroviruses. Cys-53<SUP> </SUP>was the only GP<SUB>1</SUB> (

130 kDa) cysteine residue whose replacement<SUP> </SUP>resulted in the efficient secretion of GP<SUB>1</SUB>, and it is therefore<SUP> </SUP>proposed that it participates in the formation of the only disulfide<SUP> </SUP>bond linking GP<SUB>1</SUB> to GP<SUB>2</SUB> (

24 kDa). We propose a complete cystine<SUP> </SUP>bridge map for the filovirus GPs based upon our analysis of<SUP> </SUP>mutant Ebola virus GPs. The effect of replacement of the conserved<SUP> </SUP>cysteines in the membrane-spanning region of GP<SUB>2</SUB> was found to<SUP> </SUP>depend on the nature of the substitution. Mutations in conserved<SUP> </SUP>N-linked glycosylation sites proved generally, with a few exceptions,<SUP> </SUP>innocuous. Deletion of the O-linked glycosylation region increased<SUP> </SUP>GP processing, incorporation into retrovirus particles, and<SUP> </SUP>viral transduction. Our data support a common evolutionary origin<SUP> </SUP>for the GPs of Ebola virus and avian retroviruses and have implications<SUP> </SUP>for gene transfer mediated by Ebola virus GP-pseudotyped retroviruses.

http://jvi.asm.org/cgi/content/abst...e=2/1/2002&tdate=3/31/2003&resourcetype=HWCIT