Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic
Program in Molecular Medicine; Department of Medicine
Cell Biology | Immunology of Infectious Disease | Translational Medical Research | Virology
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.
DOI of Published Version
Cell. 2016 Nov 3;167(4):1088-1098.e6. doi: 10.1016/j.cell.2016.10.014. Link to article on publisher's site
Diehl WE, Kim K, Kyawe PP, McCauley SM, Donnard E, Kucukural A, McDonel PE, Garber M, Luban J. (2016). Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic. UMass Center for Clinical and Translational Science Supported Publications. https://doi.org/10.1016/j.cell.2016.10.014. Retrieved from https://escholarship.umassmed.edu/umccts_pubs/112