title: Risks Posed by Reston, the Forgotten Ebolavirus.
abstract: Out of the five members of theEbolavirusfamily, four cause life-threatening disease, whereas the fifth, Reston virus (RESTV), is nonpathogenic in humans. The reasons for this discrepancy remain unclear. In this review, we analyze the currently available information to provide a state-of-the-art summary of the factors that determine the human pathogenicity of Ebolaviruses. RESTV causes sporadic infections in cynomolgus monkeys and is found in domestic pigs throughout the Philippines and China. Phylogenetic analyses revealed that RESTV is most closely related to the Sudan virus, which causes a high mortality rate in humans. Amino acid sequence differences between RESTV and the other Ebolaviruses are found in all nine Ebolavirus proteins, though no one residue appears sufficient to confer pathogenicity. Changes in the glycoprotein contribute to differences in Ebolavirus pathogenicity but are not sufficient to confer pathogenicity on their own. Similarly, differences in VP24 and VP35 affect viral immune evasion and are associated with changes in human pathogenicity. A recentin silicoanalysis systematically determined the functional consequences of sequence variations between RESTV and human-pathogenic Ebolaviruses. Multiple positions in VP24 were differently conserved between RESTV and the other Ebolaviruses and may alter human pathogenicity. In conclusion, the factors that determine the pathogenicity of Ebolaviruses in humans remain insufficiently understood. An improved understanding of these pathogenicity-determining factors is of crucial importance for disease prevention and for the early detection of emergent and potentially human-pathogenic RESTVs.
authors.affiliation: School of Biosciences, University of Kent, Canterbury, United Kingdom.
authors.forename: Diego
authors.initials: D
authors.lastname: Cantoni
authors.affiliation: Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis and Modelling, Imperial College London, London, United Kingdom.
authors.forename: Arran
authors.initials: A
authors.lastname: Hamlet
authors.affiliation: School of Biosciences, University of Kent, Canterbury, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.affiliation: School of Biosciences, University of Kent, Canterbury, United Kingdom.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Wass
authors.affiliation: School of Biosciences, University of Kent, Canterbury, United Kingdom.
authors.forename: Jeremy S
authors.identifier: 0000-0001-6124-4103
authors.initials: JS
authors.lastname: Rossman
keywords: Ebolavirus; Reston; pathogenicity