Archive for November 9, 2016

Human Adaptation of Ebola Virus during the West African Outbreak

Cell November 3, 2016 V.167 N.4 1079-1087

Richard A. Urbanowicz, C. Patrick McClure, Anavaj Sakuntabhai, Amadou A. Sall, Gary Kobinger13,14, Marcel A. Müller, Edward C. Holmes, Félix A. Rey, Etienne Simon-Loriere, Jonathan K. Ball

Present address: Département de microbiologie-infectiologie et d’immunologie, Université Laval, QC G1V 0A6, Canada

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA


  • EBOV adapted to humans during the West African outbreak
  • Amino acid substitutions in the EBOV glycoprotein increase human cell tropism
  • The same glycoprotein amino acid substitutions decrease tropism for bat cells


The 2013–2016 outbreak of Ebola virus (EBOV) in West Africa was the largest recorded. It began following the cross-species transmission of EBOV from an animal reservoir, most likely bats, into humans, with phylogenetic analysis revealing the co-circulation of several viral lineages. We hypothesized that this prolonged human circulation led to genomic changes that increased viral transmissibility in humans. We generated a synthetic glycoprotein (GP) construct based on the earliest reported isolate and introduced amino acid substitutions that defined viral lineages. Mutant GPs were used to generate a panel of pseudoviruses, which were used to infect different human and bat cell lines. These data revealed that specific amino acid substitutions in the EBOV GP have increased tropism for human cells, while reducing tropism for bat cells. Such increased infectivity may have enhanced the ability of EBOV to transmit among humans and contributed to the wide geographic distribution of some viral lineages.



November 9, 2016 at 8:30 am

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

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


  • 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


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.


November 9, 2016 at 8:29 am


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