Cited by 97Viral Infections and Outbreaks ResearchAdvanced Proteomics Techniques and ApplicationsVirology and Viral Diseases

Elucidation of the Ebola Virus VP24 Cellular Interactome and Disruption of Virus Biology through Targeted Inhibition of Host-Cell Protein Function

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García-Dorival, Isabel, Wu, Weining, Dowall, Stuart, Armstrong, Stuart, Touzelet, Olivier, Wastling, Jonathan, Barr, John N., Matthews, David +3 more·2014·Journal of Proteome Research

Abstract

Viral pathogenesis in the infected cell is a balance between antiviral responses and subversion of host-cell processes. Many viral proteins specifically interact with host-cell proteins to promote virus biology. Understanding these interactions can lead to knowledge gains about infection and provide potential targets for antiviral therapy. One such virus is Ebola, which has profound consequences for human health and causes viral hemorrhagic fever where case fatality rates can approach 90%. The Ebola virus VP24 protein plays a critical role in the evasion of the host immune response and is likely to interact with multiple cellular proteins. To map these interactions and better understand the potential functions of VP24, label-free quantitative proteomics was used to identify cellular proteins that had a high probability of forming the VP24 cellular interactome. Several known interactions were confirmed, thus placing confidence in the technique, but new interactions were also discovered including one with ATP1A1, which is involved in osmoregulation and cell signaling. Disrupting the activity of ATP1A1 in Ebola-virus-infected cells with a small molecule inhibitor resulted in a decrease in progeny virus, thus illustrating how quantitative proteomics can be used to identify potential therapeutic targets.

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Authors
García-Dorival, I., Wu, W., Dowall, S., Armstrong, S., Touzelet, O., Wastling, J., Barr, J. N., Matthews, D., Carroll, M., Hewson, R., & Hiscox, J. A.
Affiliations
  • University of Liverpool (GB)
  • Public Health England (GB)
  • University of Leeds (GB)
  • University of Bristol (GB)
Corresponding author
  • Hewson, Roger
  • Hiscox, Julian A.
Venue
Journal of Proteome Research
Published
2014-10-23
Volume
13
Issue
11
Pages
5120-5135
ISSN
  • 1535-3893 (ISSN-L)
  • 1535-3907
OpenAlex
W1976766564
Cited by
97
References
30
Citations by year
2026: 2 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 13 · 2020: 13 · 2019: 5 · 2018: 9 · 2017: 4 · 2016: 12 · 2015: 10 · 2014: 8
FWCI
7.94
Type
journal article
Language
en
Open access
Locations
  • Journal of Proteome Research (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • Explore Bristol Research (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • Keele Research Repository (Keele University) (submittedVersion, cc-by)
  • Bristol Research (University of Bristol) (submittedVersion)
Funders
National Institute for Health Research
Topics
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
Ebola virus, host-virus interaction, protein-protein interaction network, ATP1A1, host shutoff, immune evasion, antiviral drug targets, small molecule inhibitors, quantitative proteomics, viral hemorrhagic fever
MeSH terms
Sodium-Potassium-Exchanging ATPase, Cell Line, Humans, Ouabain, Mass Spectrometry, Viral Proteins, Reproducibility of Results, Protein Interaction Mapping, Ebolavirus, Proteomics, Green Fluorescent Proteins, Host-Pathogen Interactions, HEK293 Cells

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