The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo.

Among the Ebola viruses most species cause severe hemorrhagic fever in humans; however, Reston ebolavirus (REBOV) has not been associated with human disease despite numerous documented infections. While the molecular basis for this difference remains unclear, in vitro evidence has suggested a role f...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Allison Groseth, Andrea Marzi, Thomas Hoenen, Astrid Herwig, Don Gardner, Stephan Becker, Hideki Ebihara, Heinz Feldmann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/835ee4875e3c44228c2249d9b9ebd927
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:835ee4875e3c44228c2249d9b9ebd927
record_format	dspace
spelling	oai:doaj.org-article:835ee4875e3c44228c2249d9b9ebd9272021-11-18T06:04:07ZThe Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo.1553-73661553-737410.1371/journal.ppat.1002847https://doaj.org/article/835ee4875e3c44228c2249d9b9ebd9272012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22876185/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Among the Ebola viruses most species cause severe hemorrhagic fever in humans; however, Reston ebolavirus (REBOV) has not been associated with human disease despite numerous documented infections. While the molecular basis for this difference remains unclear, in vitro evidence has suggested a role for the glycoprotein (GP) as a major filovirus pathogenicity factor, but direct evidence for such a role in the context of virus infection has been notably lacking. In order to assess the role of GP in EBOV virulence, we have developed a novel reverse genetics system for REBOV, which we report here. Together with a previously published full-length clone for Zaire ebolavirus (ZEBOV), this provides a unique possibility to directly investigate the role of an entire filovirus protein in pathogenesis. To this end we have generated recombinant ZEBOV (rZEBOV) and REBOV (rREBOV), as well as chimeric viruses in which the glycoproteins from these two virus species have been exchanged (rZEBOV-RGP and rREBOV-ZGP). All of these viruses could be rescued and the chimeras replicated with kinetics similar to their parent virus in tissue culture, indicating that the exchange of GP in these chimeric viruses is well tolerated. However, in a mouse model of infection rZEBOV-RGP demonstrated markedly decreased lethality and prolonged time to death when compared to rZEBOV, confirming that GP does indeed contribute to the full expression of virulence by ZEBOV. In contrast, rREBOV-ZGP did not show any signs of virulence, and was in fact slightly attenuated compared to rREBOV, demonstrating that GP alone is not sufficient to confer a lethal phenotype or exacerbate disease in this model. Thus, while these findings provide direct evidence that GP contributes to filovirus virulence in vivo, they also clearly indicate that other factors are needed for the acquisition of full virulence.Allison GrosethAndrea MarziThomas HoenenAstrid HerwigDon GardnerStephan BeckerHideki EbiharaHeinz FeldmannPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 8, p e1002847 (2012)
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 Allison Groseth Andrea Marzi Thomas Hoenen Astrid Herwig Don Gardner Stephan Becker Hideki Ebihara Heinz Feldmann The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo.
description	Among the Ebola viruses most species cause severe hemorrhagic fever in humans; however, Reston ebolavirus (REBOV) has not been associated with human disease despite numerous documented infections. While the molecular basis for this difference remains unclear, in vitro evidence has suggested a role for the glycoprotein (GP) as a major filovirus pathogenicity factor, but direct evidence for such a role in the context of virus infection has been notably lacking. In order to assess the role of GP in EBOV virulence, we have developed a novel reverse genetics system for REBOV, which we report here. Together with a previously published full-length clone for Zaire ebolavirus (ZEBOV), this provides a unique possibility to directly investigate the role of an entire filovirus protein in pathogenesis. To this end we have generated recombinant ZEBOV (rZEBOV) and REBOV (rREBOV), as well as chimeric viruses in which the glycoproteins from these two virus species have been exchanged (rZEBOV-RGP and rREBOV-ZGP). All of these viruses could be rescued and the chimeras replicated with kinetics similar to their parent virus in tissue culture, indicating that the exchange of GP in these chimeric viruses is well tolerated. However, in a mouse model of infection rZEBOV-RGP demonstrated markedly decreased lethality and prolonged time to death when compared to rZEBOV, confirming that GP does indeed contribute to the full expression of virulence by ZEBOV. In contrast, rREBOV-ZGP did not show any signs of virulence, and was in fact slightly attenuated compared to rREBOV, demonstrating that GP alone is not sufficient to confer a lethal phenotype or exacerbate disease in this model. Thus, while these findings provide direct evidence that GP contributes to filovirus virulence in vivo, they also clearly indicate that other factors are needed for the acquisition of full virulence.
format	article
author	Allison Groseth Andrea Marzi Thomas Hoenen Astrid Herwig Don Gardner Stephan Becker Hideki Ebihara Heinz Feldmann
author_facet	Allison Groseth Andrea Marzi Thomas Hoenen Astrid Herwig Don Gardner Stephan Becker Hideki Ebihara Heinz Feldmann
author_sort	Allison Groseth
title	The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo.
title_short	The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo.
title_full	The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo.
title_fullStr	The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo.
title_full_unstemmed	The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo.
title_sort	ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/835ee4875e3c44228c2249d9b9ebd927
work_keys_str_mv	AT allisongroseth theebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT andreamarzi theebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT thomashoenen theebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT astridherwig theebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT dongardner theebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT stephanbecker theebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT hidekiebihara theebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT heinzfeldmann theebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT allisongroseth ebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT andreamarzi ebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT thomashoenen ebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT astridherwig ebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT dongardner ebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT stephanbecker ebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT hidekiebihara ebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo AT heinzfeldmann ebolavirusglycoproteincontributestobutisnotsufficientforvirulenceinvivo
_version_	1718424614771621888

The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo.

Ejemplares similares