Abstract

Ebola virus (EBOV) is a negative-sense single-stranded RNA virus that can cause high case fatality rates. EBOV has a genome of less than 20 kilobases, encodes seven genes, and thus has a limited coding capacity. As a result, Ebola virus relies on multifunctional proteins and co-opting host cell proteins to carry out essential functions. The viral protein 24 (VP24) is one of seven multifunctional proteins. For example, VP24 competitively inhibits the nuclear import of signal transducer and activator of transcription 1 (STAT1) by binding to karyopherin subunit alpha 5 (KPNA5). This interaction antagonizes host cell interferon signaling. It is also known that VP24 facilitates nucleocapsid condensation and intracellular transport of nucleocapsid. Multiple lines of evidence suggest potential new functions and regulations of VP24. Here, we use biochemical and cell biology techniques to explore the nucleocytoplasmic trafficking of VP24, and consequences thereof. This led us to elucidate the requirement of simultaneous cargo binding for nuclear import of VP24. We also report and characterize the interaction between VP24 and host cell protein complex WAVE Regulatory Complex that may be important for the intracellular transport of nucleocapsid. Our results highlight new aspects of VP24 multifunctionality and present opportunities for targeted therapeutics against EBOV.

Committee Chair

Gaya Amarasinghe

Committee Members

Christina Stallings; Daisy Leung; Megan Baldridge; Thomas Brett

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Molecular Microbiology & Microbial Pathogenesis)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

5-29-2026

Language

English (en)

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Available for download on Sunday, May 28, 2028

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Virology Commons

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