Genome

HT23 – Investigating molecular determinants of Ebola virus pathogenicity


Theater (plenary hall) September 7, 2016 2:40 pm - 3:00 pm

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Highlight talk – Theme: Genome

Abstract

Reston viruses are the only Ebolaviruses that are not pathogenic in humans. We analyzed 196 Ebolavirus genomes and identified specificity determining positions (SDPs) in all nine Ebolavirus proteins that distinguish Reston viruses from the four human pathogenic Ebolaviruses. Structural analysis revealed novel functional insights in particular for Ebolavirus proteins VP40 and VP24. The VP40 SDP P85T interferes with VP40 function by altering octamer formation. The VP40 SDP Q245P affects the structure and hydrophobic core of the protein and consequently protein function. Three VP24 SDPs (T131S, M136L, Q139R) impair VP24 binding to human karyopherin alpha5 and therefore inhibit interferon signaling. Since VP24 is critical for Ebolavirus adaptation to novel hosts, and only a few SDPs distinguish Reston virus VP24 from VP24 of other Ebolaviruses, human pathogenic Reston viruses may emerge. This is of concern since Reston viruses circulate in domestic pigs and can infect humans, possibly via airborne transmission

Authors

Mark Wass, University of Kent, United Kingdom
Miguel Juliá, University of Kent, United Kingdom
Mark Howard, University of Kent, United Kingdom
Jeremy Rossman, University of Kent, United Kingdom
Martin Michaelis, University of Kent, United Kingdom
Morena Pappalardo, University of Kent, United Kingdom

Source of publication

2016, Scientific Reports, 6:23743