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A Molecular Basis for the Increased Transmission of Ebolavirus in Recent Outbreaks

26 Pages Posted: 22 Dec 2019 Publication Status: Review Complete

See all articles by Andrew Kam Ho Wong

Andrew Kam Ho Wong

Emory University - Yerkes National Primate Research Center

Vennila Mathivanan

University of New South Wales (UNSW) - Immunovirology and Pathogenesis Program

Francesca Di Giallonardo

University of New South Wales (UNSW) - Immunovirology and Pathogenesis Program

Chantelle Ahlenstiel

University of New South Wales (UNSW) - Immunovirology and Pathogenesis Program

Stuart Grant Turville

University of New South Wales (UNSW) - Immunovirology and Pathogenesis Program

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Abstract

SummaryThe 2013-2016 West African Ebolavirus (EBOV) epidemic was the most widespread EBOV outbreak so far. We hypothesized this epidemic was driven by polymorphisms in the EBOV envelope glycoprotein (GP) that increased entry and infection efficiency. GP variants recovered during the epidemic were evaluated in human macrophages; an early cellular target infected during acute infection. The L368P polymorphism was identified to better attach to host surface receptors and confers superior fusogenicity over the prevalent A82V polymorphism in macrophages. However, the A82V polymorphism, along with D163N mutation, exhibited greater resistance to the NPC-1 antagonist U18666A, suggesting greater efficiency of NPC-1 receptor usage. As a result, both A82V and D163N have expanded tropism to better target bronchial epithelial cells. Overall, this study has revealed polymorphisms that enable cellular entry at higher efficiencies, and in multiple contexts. The L368P polymorphism is recommended as a biomarker for highly infectious macrophage-tropic EBOV, and potentially high-consequence outbreaks.

Keywords: Ebola, Ebolavirus, filovirus, outbreaks, viral entry, virology, Kivu, Makona, Public Health

Suggested Citation

Wong, Andrew Kam Ho and Mathivanan, Vennila and Di Giallonardo, Francesca and Ahlenstiel, Chantelle and Turville, Stuart Grant, A Molecular Basis for the Increased Transmission of Ebolavirus in Recent Outbreaks. Available at SSRN: https://ssrn.com/abstract=3507710 or http://dx.doi.org/10.2139/ssrn.3507710
This version of the paper has not been formally peer reviewed.

Andrew Kam Ho Wong

Emory University - Yerkes National Primate Research Center ( email )

United States

Vennila Mathivanan

University of New South Wales (UNSW) - Immunovirology and Pathogenesis Program

Australia

Francesca Di Giallonardo

University of New South Wales (UNSW) - Immunovirology and Pathogenesis Program

Australia

Chantelle Ahlenstiel

University of New South Wales (UNSW) - Immunovirology and Pathogenesis Program

Australia

Stuart Grant Turville (Contact Author)

University of New South Wales (UNSW) - Immunovirology and Pathogenesis Program

Australia

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