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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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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Knowledge of temporal virus-host interactions can identify viral or host factors that are targetable in antiviral therapeutics.
“knowledge of temporal virus–host interactions can also reveal viral or host factors that can be targeted in antiviral therapeutics.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [20]
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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.
- ORCID
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- 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
- hybrid
- doi.org
- Licence
- 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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