Ebola virus glycoprotein with increased infectivity dominated the 2013-2016 epidemic

William E. Diehl, Aaron E. Lin, Nathan D. Grubaugh, Luiz Max Carvalho, Kyusik Kim, Pyae Phyo Kyawe, Sean M. McCauley, Elisa Donnard, Alper Kucukural, Patrick McDonel, Stephen F. Schaffner, Manuel Garber, Andrew Rambaut, Kristian G. Andersen, Pardis C. Sabeti, Jeremy Luban

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)1088-1098.e6
Number of pages17
JournalCell
Volume167
Issue number4
DOIs
Publication statusPublished - 3 Nov 2016

Keywords / Materials (for Non-textual outputs)

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

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