Ectodomain shedding of the glycoprotein GP of Ebola virus

• DOI: 10.1038/sj.emboj.7600219
• Publication Date: 2004-04-22T08:51:54Z
• Authors: Olga Dolnik; Valentina Volchkova; Wolfgang Garten; Caroline Carbonnelle; Stephan Becker; Jörg Kahnt; Ute Ströher; Hans-Dieter Klenk; Viktor Volchkov
• Keywords: 0303 health sciences; Glycosylation; Guinea Pigs; Metalloendopeptidases; ADAM17 Protein; Oligonucleotides, Antisense; Protein Structure, Tertiary; Virus Shedding; 3. Good health; ADAM Proteins; Mice; Protein Subunits; 03 medical and health sciences; Viral Envelope Proteins; Chlorocebus aethiops; Animals; Humans; Vero Cells

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.