4 years ago

NRP2 and CD63 Are Host Factors for Lujo Virus Cell Entry

NRP2 and CD63 Are Host Factors for Lujo Virus Cell Entry
Thijn R. Brummelkamp, Lucas T. Jae, Tomas Kirchhausen, Vincent A. Blomen, Yi-ying Chou, Sarah H. Stubbs, Matthijs Raaben, Sean P. Whelan, John M. Dye, Ana I. Kuehne, Andrew S. Herbert


Arenaviruses cause fatal hemorrhagic disease in humans. Old World arenavirus glycoproteins (GPs) mainly engage α-dystroglycan as a cell-surface receptor, while New World arenaviruses hijack transferrin receptor. However, the Lujo virus (LUJV) GP does not cluster with New or Old World arenaviruses. Using a recombinant vesicular stomatitis virus containing LUJV GP as its sole attachment and fusion protein (VSV-LUJV), we demonstrate that infection is independent of known arenavirus receptor genes. A genome-wide haploid genetic screen identified the transmembrane protein neuropilin 2 (NRP2) and tetraspanin CD63 as factors for LUJV GP-mediated infection. LUJV GP binds the N-terminal domain of NRP2, while CD63 stimulates pH-activated LUJV GP-mediated membrane fusion. Overexpression of NRP2 or its N-terminal domain enhances VSV-LUJV infection, and cells lacking NRP2 are deficient in wild-type LUJV infection. These findings uncover this distinct set of host cell entry factors in LUJV infection and are attractive focus points for therapeutic intervention.

Publisher URL: http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30437-7

DOI: 10.1016/j.chom.2017.10.002

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