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  • The EMBO Journal (2004) 23, 2175 - 2184
  • doi:10.1038/sj.emboj.7600219

Published online: 22 April 2004

Ectodomain shedding of the glycoprotein GP of Ebola virus

Olga Dolnik1,2, Valentina Volchkova2, Wolfgang Garten1, Caroline Carbonnelle2, Stephan Becker1, Jörg Kahnt3, Ute Ströher1, Hans-Dieter Klenk1 and Viktor Volchkov2

  1. Institut für Virologie, Philipps-Universität Marburg, Marburg, Germany
  2. Filovirus Laboratory, University Claude Bernard Lyon-1, INSERM U412, IFR128, Lyon, France
  3. Max-Planck-Institut für terrestrische Mikrobiologie, Marburg, Germany

Correspondence to:

Viktor Volchkov, Filovirus Laboratory, University Claude Bernard Lyon-1, INSERM U412, 21 avenue Tony Garnier, 69365 Lyon, France. Tel.: +33 437 28 2450; Fax: +33 437 28 2459; E-mail: volchkov@cervi-lyon.inserm.fr

Received 14 October 2003; Accepted 2 April 2004

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 (GP2Delta) 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.

  • Keywords:

    • Ebola virus,
    • ectodomain shedding,
    • glycoprotein,
    • TACE