NRP2 and CD63 Are Host Factors for Lujo Virus Cell Entry

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. U...

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Vydáno v:Cell host & microbe Ročník 22; číslo 5; s. 688
Hlavní autoři: Raaben, Matthijs, Jae, Lucas T, Herbert, Andrew S, Kuehne, Ana I, Stubbs, Sarah H, Chou, Yi-Ying, Blomen, Vincent A, Kirchhausen, Tomas, Dye, John M, Brummelkamp, Thijn R, Whelan, Sean P
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 08.11.2017
Témata:
Carrier Proteins
Cell Line
Host-Pathogen Interactions - physiology
Human Umbilical Vein Endothelial Cells
Humans
Lujo virus - genetics
Lujo virus - pathogenicity
Lujo virus - physiology
Neuropilin-2 - metabolism
Protein Interaction Domains and Motifs
Receptors, Cell Surface - metabolism
Receptors, Transferrin
Tetraspanin 30 - metabolism
Viral Fusion Proteins - genetics
Viral Fusion Proteins - metabolism
Viral Proteins - genetics
Viral Proteins - metabolism
Virus Internalization
CD63
arenavirus
NRP2
Lujo virus
LUJV
haploid genetics
entry receptor
ISSN:1934-6069, 1934-6069
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Shrnutí: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.
Bibliografie:ObjectType-Article-1
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ISSN:1934-6069
1934-6069
DOI:10.1016/j.chom.2017.10.002