Mechanical force sensing drives extrusion of Enterovirus-A71-infected cells from colonic epithelial organoids
Abstract/Contents
- Abstract
- Enterovirus A71 (EV-A71) can cause severe disease upon systemic infection, sometimes leading to severe neurological dysfunction. However, in most cases infection is limited to the gastrointestinal tract, where virus is amplified for transmission. In this work described in this thesis, we sought to utilize three-dimensional epithelial organoids generated from crypt stem cells of healthy patient colon tissue (colonoids) to investigate viral spread through the gastrointestinal epithelium, the tissue most relevant for viral transmission. Chapter 1 introduces the reader to the viral and tissue model systems relevant for this work. In Chapter 2, the generation and characterization of an apical-out, differentiated colonoid model for EV-A71 infection is described. Chapter 3 details the surprising phenomenon of whole-cell extrusion of virus-infected cells from intact colonoids, including the timing and frequencies of these events. Poliovirus-infected cells were also readily observed extruding from gastrointestinal organoids, suggesting this phenomenon occurs during infection with multiple Enterovirus species. Chapter 4 explores the mechanism for extrusion of EV-A71-infected cells and the identification of mechanical force-sensing ion channels as required for the removal of infected cells from organoids. Finally, in Chapter 5 we explore the potential benefits of extruding a virus-infected cell for both the virus and the host. We find the extruded cells themselves are infectious, capable of initiating new infections in both monolayers and colonoid cultures. These results suggest a novel mechanism for extrusion of live, virus-infected cells through mechanical cell compression forces. In the gastrointestinal tract, apically extruded cells are released into the lumen of the gut and eventually excreted in feces; therefore, extruded infected cells likely contribute to virus spread both throughout an infected host and between hosts.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Moshiri, Jasmine Shannon |
|---|---|
| Degree supervisor | Kirkegaard, Karla |
| Thesis advisor | Kirkegaard, Karla |
| Thesis advisor | Amieva, Manuel |
| Thesis advisor | Carette, Jan, 1971- |
| Thesis advisor | Li, Jin (Billy) |
| Degree committee member | Amieva, Manuel |
| Degree committee member | Carette, Jan, 1971- |
| Degree committee member | Li, Jin (Billy) |
| Associated with | Stanford University, Department of Microbiology and Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Jasmine Shannon Moshiri. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/yg969sk8851 |
Access conditions
- Copyright
- © 2022 by Jasmine Shannon Moshiri
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...