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

Author:

Halfmann Peter J1,Borisevich Viktoriya23,Levine Corri B23,Mire Chad E23,Fenton Karla A23,Geisbert Thomas W23ORCID,Kawaoka Yoshihiro1456,Cross Robert W23

Affiliation:

1. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin–Madison

2. Department of Microbiology and Immunology

3. Galveston National Laboratory, University of Texas Medical Branch , Galveston

4. Division of Virology, Institute of Medical Science, University of Tokyo

5. Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute , Tokyo

6. Pandemic Preparedness, Infection and Advanced Research Center, University of Tokyo , Japan

Abstract

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-Δmucin. Conclusions The EBOV MLD does not play a critical role in acute pathogenesis of EVD in ferrets.

Funder

Department of Microbiology and Immunology, UTMB

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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