García-Dorival, I and Wu, W and Dowall, S and Armstrong, S and Touzelet, O and Wastling, J and Barr, JN and Matthews, D and Carroll, M and Hewson, R and Hiscox, JA (2014) Elucidation of the Ebola virus VP24 cellular interactome and disruption of virus biology through targeted inhibition of host-cell protein function. Journal of Proteome Research, 13 (11). 5120 - 5135. ISSN 1535-3907

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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.

Item Type: Article
Uncontrolled Keywords: Ebola virus, VP24 protein, antiviral, inhibitor, interactome, label free proteomics, proteomics, virus, Cell Line, Ebolavirus, Green Fluorescent Proteins, HEK293 Cells, Host-Pathogen Interactions, Humans, Mass Spectrometry, Ouabain, Protein Interaction Mapping, Proteomics, Reproducibility of Results, Sodium-Potassium-Exchanging ATPase, Viral Proteins
Subjects: ?? Cell Line ??
?? Ebola virus ??
?? Ebolavirus ??
?? Green Fluorescent Proteins ??
?? HEK293 Cells ??
?? Host-Pathogen Interactions ??
?? Humans ??
?? Mass Spectrometry ??
?? Ouabain ??
?? Protein Interaction Mapping ??
?? Proteomics ??
Q Science > QH Natural history
Q Science > QR Microbiology
?? Reproducibility of Results ??
?? Sodium-Potassium-Exchanging ATPase ??
?? VP24 protein ??
?? Viral Proteins ??
?? antiviral ??
?? inhibitor ??
?? interactome ??
?? label free proteomics ??
?? proteomics ??
?? virus ??
Divisions: Faculty of Natural Sciences > School of Life Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 18 May 2017 08:45
Last Modified: 18 May 2017 08:45
URI: http://eprints.keele.ac.uk/id/eprint/3465

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