title: Ectodomain shedding of the glycoprotein GP of Ebola virus.
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.
authors.affiliation: Institut für Virologie, Philipps-Universität Marburg, Marburg, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Dolnik
authors.forename: Valentina
authors.initials: V
authors.lastname: Volchkova
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Garten
authors.forename: Caroline
authors.initials: C
authors.lastname: Carbonnelle
authors.forename: Stephan
authors.initials: S
authors.lastname: Becker
authors.forename: Jörg
authors.initials: J
authors.lastname: Kahnt
authors.forename: Ute
authors.initials: U
authors.lastname: Ströher
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Klenk
authors.forename: Viktor
authors.initials: V
authors.lastname: Volchkov
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000818:Animals; D002522:Chlorocebus aethiops; D006031:Glycosylation; D006168:Guinea Pigs; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017201:Virus Shedding
chemical_list: D016376:Oligonucleotides, Antisense; D021122:Protein Subunits; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse