Schematic representation of the proposed NiV-F activation model.

Upon viral attachment, the ephrin receptor-mediated re-arrangements of NiV-G exert a triggering disturbance at an exposed “priming site” (presumably via direct G-F priming-site interactions) that is sufficient to activate one F glycoprotein trimer and trigger its transition from a pre-fusion to a post-fusion conformation. The transformation of a single F trimer within the hexameric assembly would disrupt its interactions with both of its neighbors, unlocking their “priming sites” and facilitating their pre-to-post fusion transitions. Thus a single ephrin/NiV-G/F trimer interaction would result in the synergetic switch from a pre-fusion to a post-fusion conformation in all six F trimers within the hexameric assembly. The resulting eighteen copies of the six-helical post-fusion F bundle would form a stable fusion pore allowing virus entry into the host cell.