Degree
Master of Science
Program
Microbiology and Immunology
Supervisor
Barr, Stephen
Abstract
Ebola’s severe pathogenesis can be attributed to its suppression of the Type I interferon (IFN) response, suggesting this pathway plays a role in restricting viral replication. One IFN-induced protein, HERC5, warrants further investigation as it inhibits the replication of evolutionarily diverse viruses. We showed that HERC5 drastically reduces the expression of structural protein VP40 at the protein and mRNA level. Mutagenesis of HERC5 demonstrated that the RCC-1-like domain is necessary and sufficient for restriction. This domain is also responsible for HERC5’s interaction with ZAP, a protein required for VP40 mRNA degradation. Finally, we showed that Ebola GP antagonizes HERC5 activity. Overall, we have identified a novel antiviral mechanism targeting Ebola RNA. Moreover, depletion of viral RNA via the RCC-1 like domain identifies a previously unknown function for HERC5. Moving forward, this information is crucial in building a solid foundation of knowledge regarding EBOV’s interaction with the IFN response during infection.
Recommended Citation
Hunt, Nina, "Interferon-induced HERC5 is a novel and potent inhibitor of Ebola virus-like particle production" (2018). Electronic Thesis and Dissertation Repository. 5922.
https://ir.lib.uwo.ca/etd/5922