Elucidation of the Ebola virus VP24 cellular interactome and disruption of virus biology through targeted inhibition of host cell protein function

Viral pathogenesis in the infected cell is a balance between anti-viral responses and subversion of host cell processes. Many viral proteins specifically interact with host cell proteins in order to promote virus biology. Understanding these interactions can lead to knowledge gains about infection and provide potential targets for anti-viral therapy. One such virus is Ebola that has profound consequences for human health, and causes viral haemorrhagic 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 signalling. 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.