The Makona Variant of Ebola Virus Is Highly Lethal to Immunocompromised Mice and Immunocompetent Ferrets
Gary Wong1,2,3,4, Anders Leung1,3, Shihua He1
1Special Pathogens Program, Public Health Agency of Canada, Winnipeg, Manitoba.
Abstract:
During 2013-2016, a novel isolate of Ebola virus (EBOV-Makona) caused an epidemic in West Africa. The virus was distinct from known EBOV strains (EBOV-Kikwit and EBOV-Mayinga), which were responsible for previous outbreaks in Central Africa. To investigate the pathogenicity of EBOV-Makona, we engineered and rescued an early isolate (H.sapiens-wt/GIN/2014/Makona-Gueckedou-C07, called rgEBOV-C07) using an updated reverse-genetics system. rgEBOV-C07 was found to be highly pathogenic in both the knockout mouse and ferret models, with median lethal dose values of 0.078 and 0.015 plaque-forming units, respectively. Therefore, these animals are appropriate for screening potential countermeasures against EBOV-Makona without the need for species adaptation.
Insights
The 2013-2016 West Africa Ebola virus (EBOV-Makona) epidemic was studied. A rescued virus isolate (rgEBOV-C07) proved highly pathogenic in mice and ferrets, validating these models for EBOV-Makona countermeasure development.
Area of Science:
- Virology
- Infectious Diseases
- Epidemiology
Background:
- The 2013-2016 West Africa epidemic was caused by a novel Ebola virus (EBOV) strain, EBOV-Makona.
- EBOV-Makona differed genetically from previous strains like EBOV-Kikwit and EBOV-Mayinga found in Central Africa.
Purpose of the Study:
- To investigate the pathogenicity of the EBOV-Makona strain.
- To establish appropriate animal models for studying EBOV-Makona and testing potential countermeasures.
Main Methods:
- An early EBOV-Makona isolate (H.sapiens-wt/GIN/2014/Makona-Gueckedou-C07) was engineered and rescued using an updated reverse-genetics system, creating rgEBOV-C07.
- The pathogenicity of rgEBOV-C07 was assessed in knockout mouse and ferret models.
Main Results:
- The rescued virus, rgEBOV-C07, demonstrated high pathogenicity in both knockout mice (MLD50 = 0.078 PFU) and ferrets (MLD50 = 0.015 PFU).
- These findings indicate that these animal models are suitable for evaluating EBOV-Makona countermeasures.
Conclusions:
- rgEBOV-C07 accurately reflects the pathogenicity of the EBOV-Makona epidemic strain.
- Knockout mice and ferrets are validated models for screening EBOV-Makona therapeutics without requiring species adaptation.
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