Electronic Thesis and Dissertation Repository

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.

Available for download on Sunday, November 15, 2020

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Virology Commons

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