| Jan 13, 2017 Functional mutations in spike glycoprotein of Zaire ebolavirus associated with an increase in infection efficiency |
Mahoko Takahashi Ueda1†*, Yohei Kurosaki2†, Taisuke Izumi3, Yusuke Nakano3, Oloniniy K. Olamide2, Jiro Yasuda2, Yoshio Koyanagi3, Kei Sato3,4*, So Nakagawa1,5*
(1Micro/Nano Technology Center, Tokai University; 2Institute of Tropical Medicine (NEKKEN), Nagasaki University; 3Laboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University; 4CREST, Japan Science and Technology Agency; 5Department of Molecular Life Science, Tokai University School of Medicine. †Equally contributed to this study, *correspondent)
Genes to Cells 2017 doi: https://doi.org/
Abstract
Ebola virus (EBOV) is extremely virulent, and its glycoprotein (GP) is necessary for viral entry. EBOV may adapt to its new host humans during outbreaks by acquiring mutations especially in GP, which allows EBOV to spread more efficiently. To identify these evolutionary selected mutations and examine their effects on viral infectivity, we adopted experimental-phylogenetic-structural interdisciplinary approaches. In evolutionary analysis of all available Zaire ebolavirus GP sequences, we detected two codon sites under positive selection, which are located near/within the region critical for the host-viral membrane fusion, namely alanine-to-valine and threonine-to-isoleucine mutations at 82 (A82V) and 544 (T544I), respectively. The fine-scale transmission dynamics of EBOV Makona variants that caused the 2014-2015 outbreak revealed that A82V mutant was fixed in the population while T544I was not. Further pseudotype assays for the Makona GP demonstrated that the A82V mutation caused a small increase in viral infectivity (x1.8) compared with the T544I mutation (x4.3). These findings suggest that mutation fixation in EBOV GP may be associated with their increased infectivity levels; the mutant with a moderate increase in infectivity will fix. Our findings demonstrated that a driving force for Ebola virus evolution via GP may be a balance between costs and benefits of its virulence.
This study was financially supported by MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2015 Tokai University School of Medicine Research Aid, Joint Usage/Research Center program of Institute for Virus Research, Kyoto University, Japan Agency for Medical Research and Development and CREST, Japan Science and Technology Agency.
Figure 1. Schematic outline of this study