PMID- 29120745
OWN - NLM
STAT- MEDLINE
DCOM- 20180809
LR  - 20200930
IS  - 1934-6069 (Electronic)
IS  - 1931-3128 (Print)
IS  - 1931-3128 (Linking)
VI  - 22
IP  - 5
DP  - 2017 Nov 8
TI  - NRP2 and CD63 Are Host Factors for Lujo Virus Cell Entry.
PG  - 688-696.e5
LID - S1931-3128(17)30437-7 [pii]
LID - 10.1016/j.chom.2017.10.002 [doi]
AB  - Arenaviruses cause fatal hemorrhagic disease in humans. Old World arenavirus 
      glycoproteins (GPs) mainly engage alpha-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.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Raaben, Matthijs
AU  - Raaben M
AD  - Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX 
      Amsterdam, the Netherlands; Department of Microbiology and Immunobiology, Harvard 
      Medical School, Boston, MA 02115, USA.
FAU - Jae, Lucas T
AU  - Jae LT
AD  - Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX 
      Amsterdam, the Netherlands; Gene Center and Department of Biochemistry, 
      Ludwig-Maximilians-Universitat Munchen, Feodor-Lynen-Strasse 25, 81377 Munich, 
      Germany.
FAU - Herbert, Andrew S
AU  - Herbert AS
AD  - U.S. Army Medical Research Institute of Infectious Diseases, Virology Division, 
      1425 Porter Street, Fort Detrick, MD 21702-5011, USA.
FAU - Kuehne, Ana I
AU  - Kuehne AI
AD  - U.S. Army Medical Research Institute of Infectious Diseases, Virology Division, 
      1425 Porter Street, Fort Detrick, MD 21702-5011, USA.
FAU - Stubbs, Sarah H
AU  - Stubbs SH
AD  - Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 
      02115, USA.
FAU - Chou, Yi-Ying
AU  - Chou YY
AD  - Department of Cell Biology, Harvard Medical School, and Program in Cellular and 
      Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
FAU - Blomen, Vincent A
AU  - Blomen VA
AD  - Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX 
      Amsterdam, the Netherlands.
FAU - Kirchhausen, Tomas
AU  - Kirchhausen T
AD  - Department of Cell Biology, Harvard Medical School, and Program in Cellular and 
      Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
FAU - Dye, John M
AU  - Dye JM
AD  - U.S. Army Medical Research Institute of Infectious Diseases, Virology Division, 
      1425 Porter Street, Fort Detrick, MD 21702-5011, USA.
FAU - Brummelkamp, Thijn R
AU  - Brummelkamp TR
AD  - Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX 
      Amsterdam, the Netherlands; CGC.nl; CeMM Research Center for Molecular Medicine 
      of the Austrian Academy of Sciences, 1090 14 Vienna, Austria. Electronic address: 
      t.brummelkamp@nki.nl.
FAU - Whelan, Sean P
AU  - Whelan SP
AD  - Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 
      02115, USA. Electronic address: sean_whelan@hms.harvard.edu.
LA  - eng
GR  - U19 AI109740/AI/NIAID NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Cell Host Microbe
JT  - Cell host & microbe
JID - 101302316
RN  - 0 (CD63 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Neuropilin-2)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Transferrin)
RN  - 0 (Tetraspanin 30)
RN  - 0 (Viral Fusion Proteins)
RN  - 0 (Viral Proteins)
RN  - 0 (neuropilin-2, human)
SB  - IM
CIN - Cell Host Microbe. 2017 Nov 8;22(5):583-585. PMID: 29120740
MH  - Carrier Proteins
MH  - Cell Line
MH  - Host-Pathogen Interactions/physiology
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Lujo virus/genetics/pathogenicity/*physiology
MH  - Neuropilin-2/*metabolism
MH  - Protein Interaction Domains and Motifs
MH  - Receptors, Cell Surface/metabolism
MH  - Receptors, Transferrin
MH  - Tetraspanin 30/*metabolism
MH  - Viral Fusion Proteins/genetics/*metabolism
MH  - Viral Proteins/genetics/*metabolism
MH  - *Virus Internalization
PMC - PMC5821226
MID - NIHMS926330
OTO - NOTNLM
OT  - CD63
OT  - LUJV
OT  - Lujo virus
OT  - NRP2
OT  - arenavirus
OT  - entry receptor
OT  - haploid genetics
EDAT- 2017/11/10 06:00
MHDA- 2018/08/10 06:00
PMCR- 2018/02/21
CRDT- 2017/11/10 06:00
PHST- 2017/07/26 00:00 [received]
PHST- 2017/09/13 00:00 [revised]
PHST- 2017/10/06 00:00 [accepted]
PHST- 2017/11/10 06:00 [entrez]
PHST- 2017/11/10 06:00 [pubmed]
PHST- 2018/08/10 06:00 [medline]
PHST- 2018/02/21 00:00 [pmc-release]
AID - S1931-3128(17)30437-7 [pii]
AID - 10.1016/j.chom.2017.10.002 [doi]
PST - ppublish
SO  - Cell Host Microbe. 2017 Nov 8;22(5):688-696.e5. doi: 10.1016/j.chom.2017.10.002.