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

Publication date: 3 November 2016
Source:Cell, Volume 167, Issue 4
Author(s): 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
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.

Graphical abstract

Teaser

An Ebola glycoprotein mutant that arose early during the West African epidemic increases infectivity of human cells and may have contributed to increased mortality


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2fiP7cm
via IFTTT