The Structure of the Lujo Virus Spike Complex

Lujo virus is a human pathogen that emerged as the etiology agent of a deadly viral disease in Africa. While it is a member of the Arenaviridae , it is a distinct virus that does not classify with the classical ‘Old World’ or ‘New World’ groups of viruses in this family. It further utilizes neuropilin-2 (NRP2) as an entry receptor, a property that is not shared by other arenaviruses. So far, structural information is limited to the receptor binding domain of LUJV, and the overall organization of the trimeric complex, as well as the way NRP2 is recognized in the context of the complete viral spike, were unknown. Here, we present the cryo-EM structure of the complete, native, membrane-embedded spike complex of LUJV. We found that NRP2 is bound at the apex of the spike in a way that allows each trimer to engage with a single NRP2. Also, the complete receptor binding site is quaternary, depending on interactions contributed by neighboring protomers. Recognition of NRP2 involves an overlooked arginine-methionine interaction, which we have now characterized. This LUJV’s spike structure, which is the second determined structure of a complete arenaviral spike, points to similarities and differences in the structures of these viral spikes, informing vaccine design and allowing us to be better prepared to combat future outbreaks of this virus.