Dissertation
Measles virus exits human airway epithelia via cell detachment pathways
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2024
DOI: 10.25820/etd.007750
Abstract
Measles virus (MeV) is the most contagious human virus and yet, we do not understand how MeV transmits between hosts more effectively than other viruses. MeV is a respiratory virus and spreads primarily via respiratory aerosols; however, all respiratory viruses utilize this strategy. In this thesis, we investigate a series of phenomena specific to MeV that may explain the disparity between transmission of MeV and other respiratory viruses: infectious center detachment from human airway epithelia. Previous studies uncovered that MeV is exceptionally proficient at spreading cell-cell through intercellular pores in human airway epithelia (HAE). MeV cell-cell spread occurs radially and culminates in a focus of infected cells, termed an “infectious center”. MeV is the only virus that forms infectious centers in HAE. Other viruses may spread to one or two neighboring cells, but infectious centers may contain upwards of 300 cells.
In this thesis, we describe that infectious centers detach as a unit from HAE at later timepoints of infection. Detached infectious centers contain high titers of MeV and can spread virus to other cells, including those important for host-host transmission. When a person infected with MeV coughs, we suspect the exhalation may contain detached infectious centers alongside cell-free virus. MeV may be more stable within infectious centers because the cells’ plasma membranes protect the virus from host adaptive immunity and environmental conditions. We postulate infectious center detachment could help explain why MeV is so contagious as the virus may live longer on surfaces, allowing spread to more people.
Finally, we investigated how infectious center detachment is triggered and found two contributing wound healing pathways: epithelial-to-mesenchymal transition and live cell extrusion. Interestingly, MeV is not the only virus known to use these pathways to cause detachment of infected cells; however, other viral infections only lead to extrusion of individual cells. This suggests that infected cells detaching as a clump adds to the transmission potential of a virus, possibly by preventing desiccation or by delivering a large bolus of virus at once. Altogether, the process from infectious center formation to detachment may explain how MeV is the most contagious human virus.
Details
- Title: Subtitle
- Measles virus exits human airway epithelia via cell detachment pathways
- Creators
- Camilla Elisabeth Hippee
- Contributors
- Patrick Sinn (Advisor)Wendy Maury (Committee Member)Aloysius Klingelhutz (Committee Member)Matthew Nonnenmann (Committee Member)Li Wu (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Biomedical Science (Microbiology)
- Date degree season
- Summer 2024
- Publisher
- University of Iowa
- DOI
- 10.25820/etd.007750
- Number of pages
- x, 84 pages
- Copyright
- Copyright 2024 Camilla Elisabeth Hippee
- Language
- English
- Date submitted
- 05/15/2024
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (pages 74-84).
- Public Abstract (ETD)
Outbreaks of measles virus (MeV) are increasing in the U.S. and on a global scale due to dropping vaccination rates. Importantly, MeV is the most contagious human virus and requires ~95% vaccine coverage to achieve herd immunity. In this thesis, we discuss qualities of MeV infection of human airway epithelia that may explain how MeV is the most contagious human virus. This includes how MeV spreads and exits airway epithelia. Importantly, we found that MeV infection of primary human airway epithelia causes clumps of infected cells to detach as a unit from the epithelial layer. We believe that virus contained within these clumps is more resistant to environmental factors, allowing MeV to live on surfaces longer. We also describe that detachment is initiated by host wound healing pathways, suggesting that MeV takes advantage of this host response to improve its transmission capability. These observations may explain why MeV is more contagious than any other human virus.
- Academic Unit
- Biomedical Science Program
- Record Identifier
- 9984698153302771
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