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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Autores principales:	Wakako Furuyama, Kyle Shifflett, Heinz Feldmann, Andrea Marzi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/cc83fff300b74ca9a612f028f74f0da2
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spelling	oai:doaj.org-article:cc83fff300b74ca9a612f028f74f0da22021-12-02T20:00:10ZThe Ebola virus soluble glycoprotein contributes to viral pathogenesis by activating the MAP kinase signaling pathway.1553-73661553-737410.1371/journal.ppat.1009937https://doaj.org/article/cc83fff300b74ca9a612f028f74f0da22021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009937https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Ebola 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.Wakako FuruyamaKyle ShifflettHeinz FeldmannAndrea MarziPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009937 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Wakako Furuyama Kyle Shifflett Heinz Feldmann Andrea Marzi The Ebola virus soluble glycoprotein contributes to viral pathogenesis by activating the MAP kinase signaling pathway.
description	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.
format	article
author	Wakako Furuyama Kyle Shifflett Heinz Feldmann Andrea Marzi
author_facet	Wakako Furuyama Kyle Shifflett Heinz Feldmann Andrea Marzi
author_sort	Wakako Furuyama
title	The Ebola virus soluble glycoprotein contributes to viral pathogenesis by activating the MAP kinase signaling pathway.
title_short	The Ebola virus soluble glycoprotein contributes to viral pathogenesis by activating the MAP kinase signaling pathway.
title_full	The Ebola virus soluble glycoprotein contributes to viral pathogenesis by activating the MAP kinase signaling pathway.
title_fullStr	The Ebola virus soluble glycoprotein contributes to viral pathogenesis by activating the MAP kinase signaling pathway.
title_full_unstemmed	The Ebola virus soluble glycoprotein contributes to viral pathogenesis by activating the MAP kinase signaling pathway.
title_sort	ebola virus soluble glycoprotein contributes to viral pathogenesis by activating the map kinase signaling pathway.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/cc83fff300b74ca9a612f028f74f0da2
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The Ebola virus soluble glycoprotein contributes to viral pathogenesis by activating the MAP kinase signaling pathway.

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