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bioRxiv · 10.1101/329482

Structural Basis for Receptor Recognition by Lujo Virus

Cohen-Dvashi, H.·Kilimnik, I.·Diskin, R.
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Abstract

Lujo virus (LUJV) has emerged as a novel and highly fatal human pathogen. Despite its membership among the Arenaviridae, LUJV does not classify with the known Old and New World groups of that viral family. Likewise, LUJV was recently found to use neuropilin-2 (NRP2) as a cellular receptor instead of the canonical -dystroglycan (-DG) or transferrin receptor 1 (TfR1) utilized by Old World (OW) and New World (NW) arenaviruses, respectively. The emergence of a deadly new pathogen into human populations using an unprecedented entry route raises many questions regarding the mechanism of cell recognition and the risk that Arenaviruses are further diversifying their infection strategies. To provide the basis for combating LUJV in particular, and to increase our general understanding of the molecular changes that accompany an evolutionary switch to a new receptor for Arenaviruses, we used X-ray crystallography to reveal how the GP1 receptor-binding domain of LUJV (LUJVGP1) recognizes NRP2. Our structural data imply that LUJV is evolutionary closer to OW than to NW arenaviruses. Structural analysis supported by experimental validation further suggests that NRP2 recognition is metal ion dependent and that the complete NRP2 binding is formed in the context of the trimeric spike. Taken together, our data provide the mechanism for the cell attachment step of LUJV, the evolutionary relationship between the GP1 domain of this novel pathogen and other arenaviruses, and indispensable information for combating LUJV.

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Cohen-Dvashi, H., Kilimnik, I., Diskin, R.. 2018-05-24. Structural Basis for Receptor Recognition by Lujo Virus. https://doi.org/10.1101/329482

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