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

November 9, 2016 at 8:29 am

Cell November 3, 2016

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

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.

PDF

http://www.cell.com/cell/pdf/S0092-8674(16)31397-6.pdf

Entry filed under: Biología Molecular, Epidemiología, F.O.D, FIEBRE en el POST-VIAJE, FIEBRE y RASH, Infecciones emergentes, Infecciones virales, Medicina del viajero, Metodos diagnosticos, Sepsis, Update, Zoonosis. Tags: .

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