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Cell DOI:10.1016/j.cell.2016.10.014

Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic.

Publication TypeJournal Article
Year of Publication2016
AuthorsDiehl, WE, Lin, AE, Grubaugh, ND, Carvalho, LMax, Kim, K, Kyawe, PPhyo, McCauley, SM, Donnard, E, Kucukural, A, McDonel, P, Schaffner, SF, Garber, M, Rambaut, A, Andersen, KG, Sabeti, PC, Luban, J
JournalCell
Volume167
Issue4
Pages1088-1098.e6
Date Published2016 Nov 03
ISSN1097-4172
Abstract

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.

DOI10.1016/j.cell.2016.10.014
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/27814506?dopt=Abstract

Alternate JournalCell
PubMed ID27814506
PubMed Central IDPMC5115602
Grant ListUL1 TR001114 / TR / NCATS NIH HHS / United States
U01 HG007910 / HG / NHGRI NIH HHS / United States
UL1 TR001453 / TR / NCATS NIH HHS / United States
R01 AI111809 / AI / NIAID NIH HHS / United States
T32 AI007244 / AI / NIAID NIH HHS / United States
DP1 DA034990 / DA / NIDA NIH HHS / United States
U19 AI110818 / AI / NIAID NIH HHS / United States
HHSN272201400048C / AI / NIAID NIH HHS / United States