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Ebola Virus Entry and Egress in Polarized Epithelial Cells
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Ebola Virus Entry and Egress in Polarized Epithelial Cells
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Dissertation
Ebola Virus Entry and Egress in Polarized Epithelial Cells
2018
Overview
Currently, there are no approved vaccines or treatments available for Ebola virus disease and therapy remains largely supportive. Ebola virus has broad tissue tropism and can infect a variety of cells including epithelial cells. Epithelial cells differ from most other cell types in their polarized phenotype and barrier function. In polarized cells, the apical and basolateral membrane domains are demarcated by tight junctions. Polarized cells also have specialized sorting machinery, which results in a difference in composition of the two membrane domains. These specialized functions of sorting can have important consequences for viral infections. Differential localization of a viral receptor can restrict virus entry to a particular membrane while, polarized sorting can lead to a vectorial virus release. To elucidate the characteristics of Ebola virus entry and egress, in polarized cells, we first characterized the polarized colorectal adenocarcinoma cell model for the study. When grown on a semi-permeable transwell support, polarized colorectal adenocarcinoma cells form tight junction and exhibit characteristic apical and basal morphology by day 6 post seeding as evidenced by measurement of transepithelial resistance and electron microscopy respectively. Our data in the polarized colorectal adenocarcinoma cell model indicate that Ebola virus preferentially infects from the basolateral route, and this preference may be influenced by the extent of polarity. Our experiments also show that that Ebola virus is released from polarized cells preferentially through the basolateral surface without changes in cellular permeability. Further, our data shows that polarized distribution of heparan sulfate, a known viral attachment factor, may be responsible for causing the basolateral preference shown by the virus during entry in colorectal adenocarcinoma cells. Elucidating Ebola virus entry and egress in polarized cells can help in understanding the viral transmission cycle and pathogenesis.
Publisher
ProQuest Dissertations & Theses
Subject
ISBN
9780438401075, 0438401077
