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BeNeLux Bioinformatics Conference – Antwerp, December 7-8 <strong>2015</strong><br />

Abstract ID: P<br />

Poster<br />

10th Benelux Bioinformatics Conference <strong>bbc</strong> <strong>2015</strong><br />

P65. ORTHOLOGICAL ANALYSIS OF AN EBOLA VIRUS – HUMAN PPIN<br />

SUGGESTS REDUCED INTERFERENCE OF EBOLA VIRUS WITH EPIGENETIC<br />

PROCESSES IN ITS SUSPECTED BAT RESERVOIR HOST<br />

Ben Verhees 1* , Kris Laukens 1,2 , Stefan Naulaerts 1,2 , Pieter Meysman 1,2 & Xaveer Van Ostade 3 .<br />

Biomedical informatics research center Antwerpen (biomina) 1 ; Advanced Database Research and Modeling (ADReM),<br />

University of Antwerp 2 ; Laboratory of Protein Science, Proteomics and Epigenetic Signalling (PPES) and Centre for<br />

Proteomics and Mass spectrometry (CFP-CeProMa), University of Antwerp 3 . * ben.verhees@student.uantwerpen.be<br />

Ebola virus is a zoonosis, but its reservoir host has not yet been identified. Recent findings suggest however, that Mops<br />

condylurus, an insect-eating bat, is a likely candidate. Studying the interactions between Ebola virus and its reservoir<br />

host could prove highly informative, as reservoir hosts of zoonotic pathogens often appear to tolerate infections with<br />

these pathogens with little evidence of disease. In this study, a protein-protein interaction network (PPIN) was created<br />

between Ebola virus and human proteins. Orthology data in Myotis lucifugus – a model organism often used for bat<br />

studies – was employed to determine which of the human first neighbors of Ebola virus proteins do not possess an<br />

orthologue in M. lucifugus. Subsequent GO enrichment analysis suggested that these proteins are mostly involved in<br />

epigenetic processes, and thus we hypothesize that Ebola virus displays reduced interference with epigenetic processes in<br />

its reservoir host.<br />

INTRODUCTION<br />

The idea that bats serve as reservoirs for a wide range of<br />

zoonotic pathogens has been the topic of much recent<br />

research. Previous studies on human and bat orthology in<br />

this context have mainly focused on specific genes,<br />

important in fighting off viral infection.<br />

Our study is different however, in that it focuses on<br />

proteins the Ebola virus immediately interacts with in<br />

humans, and the existence of orthologues of these proteins<br />

in bats.<br />

METHODS<br />

Construction of an Ebola virus – human PPIN<br />

An Ebola virus – human PPIN was constructed from in<br />

silico data. All network analysis was done using<br />

Cytoscape v. 3.2.1.<br />

Orthology analysis<br />

Identification of orthologues was performed using the<br />

OMA orthology database, release: September <strong>2015</strong>.<br />

Statistics<br />

For the statistical analysis, the hypergeometric test was<br />

performed.<br />

GO enrichment<br />

GO enrichment analysis was performed using ClueGO v.<br />

1.2.7, a Cytoscape plug-in. Default settings were used, and<br />

all ontologies/pathways were examined.<br />

RESULTS & DISCUSSION<br />

Myotis lucifugus as a model for Mops condylurus<br />

In this study, Myotis lucifugus was used as a model to<br />

study interactions between Ebola virus and Mops<br />

condylurus, its suspected reservoir.<br />

Ebola virus – human PPIN and orthology in M.<br />

lucifugus<br />

An Ebola virus – human PPIN was created, and human<br />

first neighbors of Ebola virus proteins were examined for<br />

existence of orthologues in M. lucifugus. Statistical<br />

analysis revealed that there was an upregulation of human<br />

proteins with orthologues in M. lucifugus (p=0.019).<br />

GO enrichment suggests reduced interference of Ebola<br />

virus with epigenetic processes in its reservoir host<br />

Gene ontology (GO) enrichment analysis was performed<br />

of the human first neighbors of Ebola virus proteins which<br />

do not possess an orthologue in M. lucifugus. The analysis<br />

revealed that these proteins are mostly involved in<br />

epigenetic processes (Figure 1).<br />

FIGURE 1. GO enrichment analysis of human first neighbors of Ebola<br />

virus proteins which do not possess an orthologue in M. lucifugus.<br />

Discussion<br />

Using this novel approach, we have shown that Ebola<br />

virus is likely able to interfere with epigenetic processes in<br />

humans. Secondly, Ebola virus’ ability to interfere with<br />

host epigenetics is likely reduced or altered in its reservoir<br />

host.<br />

While the idea that viruses are able to interact with host<br />

epigenetic mechanisms is fairly recent, over the past few<br />

years significant research has been done exploring this<br />

topic. In a comprehensive review, Li et al. (2014) describe<br />

how specific viral proteins are able to modulate the<br />

activity of chromatin modification complexes, e.g. HATs,<br />

HDACs, HMTs, and HDMTs, and even directly bind<br />

histone proteins. These findings lend support to the results<br />

of our study, as these suggest that Ebola virus is also able<br />

to interact with HDACs, HMTs and several histone<br />

proteins in humans.<br />

REFERENCES<br />

Li S et al. Rev Med Virol 24, 223-241 (2014).<br />

109

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