Ectodomain shedding of the glycoprotein GP of Ebola virus

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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 (GP2Δ) subunits from the cell surface. We show that tumor necrosis factor α‐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.