Analysis of the humoral immune response against the envelope glycoprotein Gc of Schmallenberg virus reveals a domain located at the amino terminus targeted by mAbs with neutralizing activity

Orthobunyaviruses are enveloped viruses that are arthropod-transmitted and cause disease in humans and livestock. The viral attachment and entry is mediated by the envelope glycoproteins Gn and Gc, and the major glycoprotein Gc of certain orthobunyaviruses is targeted by neutralizing antibodies. The domains in which the epitopes of such antibodies are located on the glycoproteins of the animal orthobunyavirus "Schmallenberg virus (SBV)" have not been identified. Here, we analyzed the reactivity of a set of monoclonal antibodies and antisera against recombinant SBV-glycoproteins. The M-segment encoded proteins Gn and Gc of SBV were expressed as full-length proteins, and Gc was also produced as two truncated forms that comprised its amino terminal third and carboxyl terminal two thirds. The sera from convalescent animals reacted only against the full-length Gc and its subdomains but not against the SBV-glycoprotein Gn. Interestingly, the amino terminal domain of SBV-Gc was not only targeted by polyclonal sera but also by the majority of murine monoclonal antibodies with a neutralizing activity. Furthermore, the newly defined amino-terminal domain of about 230 amino-acids of the SBV-Gc-protein could be affinity-purified and further characterized. This major neutralizing domain might be relevant for the development of prophylactic, diagnostic and therapeutic approaches for SBV and other orthobunyaviruses.