The Ebola Virus Glycoprotein Contributes to but Is Not Sufficient for Virulence In Vivo

Allison Groseth, Andrea Marzi, Thomas Hoenen, Astrid Herwig, Don Gardner, Stephan Becker, Hideki Ebihara, Heinz Feldmann

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Article numbere1002847
JournalPLoS Pathogens
Volume8
Issue number8
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

Fingerprint

Ebolavirus
Virulence
Glycoproteins
Democratic Republic of the Congo
Viruses
Reverse Genetics
Virulence Factors
Virus Diseases
Infection
Fever
Clone Cells
Phenotype

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Groseth, A., Marzi, A., Hoenen, T., Herwig, A., Gardner, D., Becker, S., ... Feldmann, H. (2012). The Ebola Virus Glycoprotein Contributes to but Is Not Sufficient for Virulence In Vivo. PLoS Pathogens, 8(8), [e1002847]. https://doi.org/10.1371/journal.ppat.1002847

The Ebola Virus Glycoprotein Contributes to but Is Not Sufficient for Virulence In Vivo. / Groseth, Allison; Marzi, Andrea; Hoenen, Thomas; Herwig, Astrid; Gardner, Don; Becker, Stephan; Ebihara, Hideki; Feldmann, Heinz.

In: PLoS Pathogens, Vol. 8, No. 8, e1002847, 01.08.2012.

Research output: Contribution to journalArticle

Groseth, A, Marzi, A, Hoenen, T, Herwig, A, Gardner, D, Becker, S, Ebihara, H & Feldmann, H 2012, 'The Ebola Virus Glycoprotein Contributes to but Is Not Sufficient for Virulence In Vivo', PLoS Pathogens, vol. 8, no. 8, e1002847. https://doi.org/10.1371/journal.ppat.1002847
Groseth A, Marzi A, Hoenen T, Herwig A, Gardner D, Becker S et al. The Ebola Virus Glycoprotein Contributes to but Is Not Sufficient for Virulence In Vivo. PLoS Pathogens. 2012 Aug 1;8(8). e1002847. https://doi.org/10.1371/journal.ppat.1002847
Groseth, Allison ; Marzi, Andrea ; Hoenen, Thomas ; Herwig, Astrid ; Gardner, Don ; Becker, Stephan ; Ebihara, Hideki ; Feldmann, Heinz. / The Ebola Virus Glycoprotein Contributes to but Is Not Sufficient for Virulence In Vivo. In: PLoS Pathogens. 2012 ; Vol. 8, No. 8.
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