PMID- 34529738
OWN - NLM
STAT- MEDLINE
DCOM- 20211124
LR  - 20211124
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 17
IP  - 9
DP  - 2021 Sep
TI  - The Ebola virus soluble glycoprotein contributes to viral pathogenesis by 
      activating the MAP kinase signaling pathway.
PG  - e1009937
LID - 10.1371/journal.ppat.1009937 [doi]
LID - e1009937
AB  - Ebola virus (EBOV) expresses three different glycoproteins (GPs) from its GP 
      gene. The primary product, soluble GP (sGP), is secreted in abundance during 
      infection. EBOV sGP has been discussed as a potential pathogenicity factor, 
      however, little is known regarding its functional role. Here, we analyzed the 
      role of sGP in vitro and in vivo. We show that EBOV sGP has two different 
      functions that contribute to infectivity in tissue culture. EBOV sGP increases 
      the uptake of virus particles into late endosomes in HEK293 cells, and it 
      activates the mitogen-activated protein kinase (MAPK) signaling pathway leading 
      to increased viral replication in Huh7 cells. Furthermore, we analyzed the role 
      of EBOV sGP on pathogenicity using a well-established mouse model. We found an 
      sGP-dependent significant titer increase of EBOV in the liver of infected 
      animals. These results provide new mechanistic insights into EBOV pathogenicity 
      and highlight EBOV sGP as a possible therapeutic target.
FAU - Furuyama, Wakako
AU  - Furuyama W
AUID- ORCID: 0000-0001-7163-6960
AD  - Laboratory of Virology, Division of Intramural Research, National Institute of 
      Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain 
      Laboratories, Hamilton, Montana, United States of America.
FAU - Shifflett, Kyle
AU  - Shifflett K
AD  - Laboratory of Virology, Division of Intramural Research, National Institute of 
      Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain 
      Laboratories, Hamilton, Montana, United States of America.
FAU - Feldmann, Heinz
AU  - Feldmann H
AUID- ORCID: 0000-0001-9448-8227
AD  - Laboratory of Virology, Division of Intramural Research, National Institute of 
      Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain 
      Laboratories, Hamilton, Montana, United States of America.
FAU - Marzi, Andrea
AU  - Marzi A
AUID- ORCID: 0000-0003-0186-9587
AD  - Laboratory of Virology, Division of Intramural Research, National Institute of 
      Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain 
      Laboratories, Hamilton, Montana, United States of America.
LA  - eng
SI  - figshare/10.6084/m9.figshare.16587158.v1
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20210916
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Viral Proteins)
RN  - 0 (Virulence Factors)
SB  - IM
MH  - Animals
MH  - Ebolavirus/metabolism/*pathogenicity
MH  - HEK293 Cells
MH  - Hemorrhagic Fever, Ebola/*metabolism
MH  - Humans
MH  - MAP Kinase Signaling System/*physiology
MH  - Mice
MH  - Viral Proteins/*metabolism
MH  - Virulence Factors/metabolism
MH  - Virus Replication/*physiology
PMC - PMC8478236
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/09/17 06:00
MHDA- 2021/11/25 06:00
PMCR- 2021/09/16
CRDT- 2021/09/16 17:24
PHST- 2021/02/16 00:00 [received]
PHST- 2021/09/02 00:00 [accepted]
PHST- 2021/09/28 00:00 [revised]
PHST- 2021/09/17 06:00 [pubmed]
PHST- 2021/11/25 06:00 [medline]
PHST- 2021/09/16 17:24 [entrez]
PHST- 2021/09/16 00:00 [pmc-release]
AID - PPATHOGENS-D-21-00355 [pii]
AID - 10.1371/journal.ppat.1009937 [doi]
PST - epublish
SO  - PLoS Pathog. 2021 Sep 16;17(9):e1009937. doi: 10.1371/journal.ppat.1009937. 
      eCollection 2021 Sep.