@article{cdf3b015237144e7b766a0997c37cfb6,
title = "NRP2 and CD63 Are Host Factors for Lujo Virus Cell Entry",
abstract = "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. Raaben et al. demonstrate that the semaphorin and VEGF receptor NRP2 also functions as an entry receptor for Lujo virus, a causative agent of lethal hemorrhagic fever in humans. In addition, the molecule CD63 was identified as an intracellular factor facilitating membrane fusion mediated by the Lujo virus glycoprotein.",
keywords = "CD63, LUJV, Lujo virus, NRP2, arenavirus, entry receptor, haploid genetics",
author = "Matthijs Raaben and Jae, {Lucas T.} and Herbert, {Andrew S.} and Kuehne, {Ana I.} and Stubbs, {Sarah H.} and Chou, {Yi ying} and Blomen, {Vincent A.} and Tomas Kirchhausen and Dye, {John M.} and Brummelkamp, {Thijn R.} and Whelan, {Sean P.}",
note = "Funding Information: We thank E.O. Saphire (Scripps Research Institute) for providing cDNA encoding the LUJV GP precursor, as well as the expression construct encoding Fc-tagged LUJV GP1, and the members of the Brummelkamp and Whelan laboratories for helpful discussions. We also thank Kathleen Cashman (USAMRIID) for providing the arenavirus NP-specific polyclonal guinea pig serum and John Hilkens (Netherlands Cancer Institute) for sharing anti-human TfR antibodies (clone 66Ig10). This work was supported by a Marie Sklodowska-Curie Action fellowship ( H2020-MSCA-IF-2014 660417 ) to M.R., by Defense Threat Reduction Agency funding ( CB4088 ) to J.M.D., by National Institutes of Health funding ( AI109740 ) to S.P.W. and T.K., and by a European Research Council (ERC) Starting Grant ( ERC-2012-StG 309634 ) to T.R.B. Opinions, conclusions, interpretations, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. The mention of trade names or commercial products does not constitute endorsement or recommendation for use by the Department of the Army or the Department of Defense. T.R.B. is co-founder and SAB member of Haplogen and co-founder and Managing Director of Scenic Biotech. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = nov,
day = "8",
doi = "10.1016/j.chom.2017.10.002",
language = "English",
volume = "22",
pages = "688--696.e5",
journal = "Cell Host and Microbe",
issn = "1931-3128",
number = "5",
}