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Presence of Ebola Structural Proteins in Exosomes Can Cause Immune System Dysregulation

Date

2015-12-11

Authors

Heath, Allison

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Abstract

The Ebola virus (EBOV) is a member of the Filoviridae family and is the virus responsible for the most recent world health emergency. The first outbreaks of the disease occurred in 1976 in Sudan and in the Democratic Republic of Congo. The most recent outbreak has included the countries of Guinea, Sierra Leone, Liberia, Nigeria, Mali and Senegal. Within days of infection with the virus, patients begin to experience fever, chills, and myalgia. As the infection progresses, symptoms advance to nausea, vomiting, diarrhea, chest pain, cough, bloody feces, vomiting blood, distention and/or hemorrhage of sclerotic arterioles in the eyes, gastrointestinal bleeding from the mouth and rectum and hemorrhage from the nose and mouth may also be observed. Spread of the virus occurs through breaks in the skin, contact with mucosal surfaces, or after direct contact with persons infected or recently deceased from the virus. It is crucial that we gain a greater understanding of the mechanisms of the pathenogenesis of this virus; both to prevent future outbreaks of the disease and to better understand other similar RNA viruses. In this project, we have focused on biology of three proteins critical for Ebola pathogenesis. Ebola GP, NP and VP40 are proteins associated with egress and entry into the cells. Our data suggests that exposure of VP40 to immune cells can result in cell death, and that this protein may be transmitted via exosomes. Our study aids in deciphering the role of VP40 in immune cell death and suggests that some FDA approved drugs that inhibit the cell death may reverse at least some pathogenic processes instigated by the VP40 associated exosomes. While the effects of exosomes on the course of viral infection and host response have yet to be fully explored, we have provided evidence that these exosomes may play a role in the spread of Ebola infection to immune privileged sites and a possibility of the establishment of latent Ebola infection.

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Keywords

Exosome, Dysregulation, Immune inhibition, Ebola

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