A Molecular Basis for the Increased Transmission of Ebolavirus in Recent Outbreaks
26 Pages Posted: 22 Dec 2019 Publication Status: Review Complete
More...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
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