Ectodomain shedding of the glycoprotein GP of Ebola virus

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 shed-dases. Proteolytic cleavage taking place at amino-acid position D-637 removes the transmembrane anchor and liberates complexes consisting of GP(1) and truncated GP(2) (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.