Date of Award

2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Cell & Molecular Biology

First Advisor

Paul Bates

Abstract

The 2014-2016 West Africa epidemic was the worst Ebola virus outbreak on record, with the infected numbering over 28,000 and the dead more than 11,000. Among those who survived the disease, Ebola virus was found to persist in numerous anatomical locations and be shed in semen. During the West Africa outbreak, numerous occurrences of Ebola sexual transmission were documented. While sexual transmission has the potential to compromise public health eradication efforts and reignite outbreaks, no molecular details of host factors influencing this phenomenon are known. Amyloid fibrils present in healthy individuals’ semen have been suggested to be a host factor that aids in sexual transmission of viruses including HIV-1. To understand if seminal amyloid fibrils increase infection by Ebola virus, a recombinant virus expressing the Ebola glycoprotein was preincubated with the type species of the seminal amyloids, SEVI. When present, SEVI resulted in a nearly 20-fold increase in infection of physiologically relevant target cells. SEVI and other seminal amyloids were also found to enhance authentic Ebola virus infection by 20- to 40-fold in cell culture. Mechanistically, SEVI was found to increase viral attachment then subsequent internalization of virus through macropinocytosis, a previously unknown ability to enhance uptake by this mechanism critical for Ebola virus entry. Finally, a new ability of SEVI to enhance viral stability during incubation at physiologic temperatures and under desiccating conditions is described, a finding important for transmission biology. Together, these functions of seminal amyloids represent a first step toward understanding Ebola virus sexual transmission at a molecular level and provide potential therapeutic targets to prevent transmission by this route.

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