Cell
Volume 167, Issue 4, 3 November 2016, Pages 1088-1098.e6
Journal home page for Cell

Article
Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013–2016 Epidemic

https://doi.org/10.1016/j.cell.2016.10.014Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Ebola glycoprotein mutant GP-A82V arose early and dominated the West African epidemic

  • GP-A82V infects human cells more efficiently than does the ancestral glycoprotein

  • The increased infectivity of GP-A82V is specific for primate cells

  • GP-A82V was weakly associated with increased mortality during the epidemic

Summary

The magnitude of the 2013–2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymous mutation, Ebola virus (EBOV) glycoprotein (GP) mutant A82V, for its effect on viral infectivity. This mutation, located at the NPC1-binding site on EBOV GP, occurred early in the 2013–2016 outbreak and rose to high frequency. We found that GP-A82V had heightened ability to infect primate cells, including human dendritic cells. The increased infectivity was restricted to cells that have primate-specific NPC1 sequences at the EBOV interface, suggesting that this mutation was indeed an adaptation to the human host. GP-A82V was associated with increased mortality, consistent with the hypothesis that the heightened intrinsic infectivity of GP-A82V contributed to disease severity during the EVD epidemic.

Keywords

Ebola virus
epidemic
mutation
NPC1
glycoprotein
outbreak
RNA virus
Filovirus
adaptation
infection

Cited by (0)

9

Co-first author

10

Lead Contact