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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.

Original publication

DOI

10.1021/pr500556d

Type

Journal article

Journal

Journal of proteome research

Publication Date

11/2014

Volume

13

Pages

5120 - 5135

Addresses

Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool , Liverpool L3 5RF, United Kingdom.

Keywords

Cell Line, Humans, Ouabain, Green Fluorescent Proteins, Viral Proteins, Reproducibility of Results, Protein Interaction Mapping, Proteomics, Mass Spectrometry, Ebolavirus, Sodium-Potassium-Exchanging ATPase, Host-Pathogen Interactions, HEK293 Cells