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PMID: 15103332 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Ectodomain shedding of the glycoprotein GP of Ebola virus.

The EMBO journal ·Vol. 23 ·No. 10 ·2004-05-19 ·Pages 2175-84

Dolnik O, Volchkova V, Garten W, Carbonnelle C, Becker S, Kahnt J, Ströher U, Klenk HD, Volchkov V

Abstract

In this study, release of abundant amounts of the Ebola virus (EBOV) surface glycoprotein GP in a soluble form from virus-infected cells was investigated. We demonstrate that the mechanism responsible for the release of GP is ectodomain shedding mediated by cellular sheddases. Proteolytic cleavage taking place at amino-acid position D637 removes the transmembrane anchor and liberates complexes consisting of GP1 and truncated GP2 (GP(2delta)) subunits from the cell surface. We show that tumor necrosis factor alpha-converting enzyme (TACE), a member of the ADAM family of zinc-dependent metalloproteases, is involved in EBOV GP shedding. This finding shows for the first time that virus-encoded surface glycoproteins are substrates for ADAMs. Furthermore, we provide evidence that shed GP is present in significant amounts in the blood of virus-infected animals and that it may play an important role in the pathogenesis of infection by efficiently blocking the activity of virus-neutralizing antibodies.

MeSH Terms
ADAM Proteins ADAM17 Protein Animals Chlorocebus aethiops Glycosylation Guinea Pigs Humans Metalloendopeptidases/metabolism Mice Oligonucleotides, Antisense/genetics,metabolism Protein Structure, Tertiary Protein Subunits/genetics,metabolism Vero Cells Viral Envelope Proteins/chemistry,genetics,metabolism Virus Shedding
Chemicals
Oligonucleotides, Antisense Protein Subunits Viral Envelope Proteins envelope glycoprotein, Ebola virus ADAM Proteins Metalloendopeptidases ADAM17 Protein ADAM17 protein, human Adam17 protein, mouse
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Dolnik Olga
Institut für Virologie, Philipps-Universität Marburg, Marburg, Germany.
Volchkova Valentina
Garten Wolfgang
Carbonnelle Caroline
Becker Stephan
Kahnt Jörg
Ströher Ute
Klenk Hans-Dieter
Volchkov Viktor
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600219
Published
2004-05-19
Epub
2004-00-22
Pages
2175-84
Language
English
Region
England
NLM ID
8208664
PMCID
PMC424403
Subset
IM
Grants
NIAID NIH HHS · R21 AI053571 · United States
NIAID NIH HHS · R21 AI53571 · United States
External Links
PubMed source DOI: 10.1038/sj.emboj.7600219 PMC Full Text View journal details
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