The Ebola virus soluble glycoprotein contributes to viral pathogenesis by activating the MAP kinase signaling pathway

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 analy...

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Bibliographic Details
Published in:PLoS pathogens 2021-09, Vol.17 (9), p.e1009937-e1009937
Main Authors: Furuyama, Wakako, Shifflett, Kyle, Feldmann, Heinz, Marzi, Andrea
Format: Article
Language:English
Subjects:
Antibodies
Biology and life sciences
Cell culture
Cellular signal transduction
Computer and Information Sciences
Development and progression
Ebola virus
Ebola virus infections
Ebolavirus
Editing
Endosomes
Engineering and Technology
Experiments
Glycoproteins
Health aspects
Infectivity
Kinases
MAP kinase
Medicine and Health Sciences
Mitogen-activated protein kinases
Pathogenesis
Pathogenicity
Pathogens
Physiological aspects
Protein kinase
Proteins
Signal transduction
Signaling
Standard deviation
Therapeutic targets
Tissue culture
Viral diseases
Viral proteins
Viruses
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1009937