Nipah virus (NiV) is a highly pathogenic emerging henipavirus for which there are no licensed vaccines or therapeutics currently available. Viral entry is mediated by the coordinated action of the attachment (NiVG) and fusion (NiVF) glycoproteins yet the organisation of NiVF on viral particles and its influence on antibody neutralisation is not completely understood. Using cryo-electron tomography of NiV pseudovirions and virus-like particles (VLPs), we directly observe inter-F contacts on viral membranes. These interactions occur frequently but are distributed stochastically, forming variably sized assemblies rather than ordered arrays, consistent with transient or low-affinity associations. We have generated single domain antibodies (termed nanobodies) to the NiVF glycoprotein that bind to an epitope at the interface between neighbouring NiVF trimers and therefore occlude the inter-NiVF contacts. We show that these nanobodies inhibit VLP cell fusion and neutralise NiV pseudoviruses in vitro, which suggests that the interaction between NiVF trimers is important for NiV virus entry. The identification of the inter-NiVF contacts on viral particles adds a previously unrecognised structural feature to the organisation of the NiV entry machinery which could be targeted to prevent viral infection.
Crisis support teams’ technological openness and learning attitudes toward the AI based virtual patient system crisis support VR
BackgroundAgainst the backdrop of escalating global humanitarian crises, innovative didactic simulations are becoming increasingly important. A promising alternative to traditional classroom-based didactics for learning psychological