The Mucin-Like Domain of the Ebola Glycoprotein Does Not Impact Virulence or Pathogenicity in Ferrets.

Peter J Halfmann, Viktoriya Borisevich, Corri B Levine, Chad E Mire, Karla A Fenton, Thomas W Geisbert, Yoshihiro Kawaoka, Robert W Cross
Author Information
  1. Peter J Halfmann: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison.
  2. Viktoriya Borisevich: Department of Microbiology and Immunology.
  3. Corri B Levine: Department of Microbiology and Immunology.
  4. Chad E Mire: Department of Microbiology and Immunology.
  5. Karla A Fenton: Department of Microbiology and Immunology.
  6. Thomas W Geisbert: Department of Microbiology and Immunology. ORCID
  7. Yoshihiro Kawaoka: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison.
  8. Robert W Cross: Department of Microbiology and Immunology.

Abstract

BACKGROUND: Ebola virus (EBOV) is considered among the most dangerous viruses with case fatality rates approaching 90% depending on the outbreak. While several viral proteins (VPs) including VP24, VP35, and the soluble glycoprotein are understood to contribute to virulence, less is known of the contribution of the highly variable mucin-like domain (MLD) of EBOV. Early studies have defined a potential role in immune evasion of the MLD by providing a glycan shield to critical glycoprotein residues tied to viral entry. Nonetheless, little is known as to what direct role the MLD plays in acute EBOV disease (EVD).
METHODS: We generated an infectious EBOV clone that lacks the MLD and assessed its virulence in ferrets compared with wild-type (WT) virus.
RESULTS: No differences in growth kinetics were observed in vitro, nor were there any differences in time to death, viremia, or clinical picture in ferrets infected with recombinant EBOV (rEBOV)-WT or rEBOV-��mucin.
CONCLUSIONS: The EBOV MLD does not play a critical role in acute pathogenesis of EVD in ferrets.

Keywords

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Grants

  1. U19 AI106772/NIAID NIH HHS
  2. U19AI106772/NIH HHS

MeSH Term

Animals
Humans
Hemorrhagic Fever, Ebola
Mucins
Virulence
Ferrets
Ebolavirus
Glycoproteins

Chemicals

Mucins
Glycoproteins

Word Cloud

Created with Highcharts 10.0.0EBOVMLDferretsEbolavirusroleviralglycoproteinvirulenceknownmucin-likedomaincriticalacuteEVDdifferencesBACKGROUND:consideredamongdangerousvirusescasefatalityratesapproaching90%dependingoutbreakseveralproteinsVPsincludingVP24VP35solubleunderstoodcontributelesscontributionhighlyvariableEarlystudiesdefinedpotentialimmuneevasionprovidingglycanshieldresiduestiedentryNonethelesslittledirectplaysdiseaseMETHODS:generatedinfectiousclonelacksassessedcomparedwild-typeWTRESULTS:growthkineticsobservedvitrotimedeathviremiaclinicalpictureinfectedrecombinantrEBOV-WTrEBOV-��mucinCONCLUSIONS:playpathogenesisMucin-LikeDomainGlycoproteinImpactVirulencePathogenicityFerretsreversegenetics

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