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Identification of important amino acid replacements in the 2013-2016 Ebola virus outbreak

By Abayomi S Olabode, Derek Gatherer, Xiaowei Jiang, David Matthews, Julian Alexander Hiscox, Stephan Gunther, Miles W Carroll, Simon C Lovell, David L Robertson

Posted 14 Sep 2016
bioRxiv DOI: 10.1101/075168

The phylogenetic relationships of Zaire ebolavirus have been intensively analysed over the course of the 2013-2016 outbreak. However, there has been limited consideration of the functional impact of this variation. Here we describe an analysis of the available sequence data in the context of protein structure and phylogenetic history. Amino acid replacements are rare and predicted to have minor effects on protein stability. Synonymous mutations greatly outnumber nonsynonymous mutations, and most of the latter fall into unstructured intrinsically disordered regions, indicating that purifying selection is the dominant mode of selective pressure. However, one replacement, occurring early in the outbreak in Gueckedou in Guinea on 31st March 2014 (alanine to valine at position 82 in the GP protein), is close to the site where the virus binds to the host receptor NPC1 and is located in the phylogenetic tree at the origin of the major B lineage of the outbreak. The functional and evolutionary evidence indicates this A82V change likely has consequences for EBOV's host specificity and hence adaptation to humans.

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