- Title
- Innate anti-viral responses of airway epithelial cells to infection with rhinovirus and coronavirus
- Creator
- Loo, Su-Ling
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2018
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- The “common cold,” caused by respiratory viruses such as rhinovirus (RV) and coronavirus (CoV), is a significant clinical burden worldwide. For those with chronic airways disease, such as chronic obstructive pulmonary disease (COPD), a simple cold can lead to exacerbations, hospitalisation and even death. In addition, the emergence of pathogenic coronaviruses from animal reservoirs - such as SARS-CoV and MERS-CoV – are a potential cause of pandemics. In the lung, the airway epithelium forms the first line of defence that involves the expression of innate pathogen-recognition receptors (PRRs). Once a viral pathogen is recognised, downstream transcription factors are activated, leading to the production of interferons (IFNs). These IFNs initiate signalling cascades that limit viral infection. In addition, the phosphoinositide 3-kinase (PI3K) signalling pathway is also involved in innate immune processes and has been implicated to be utilised by viruses such as Influenza A, especially in COPD. This thesis aims to elucidate some of the mechanisms that underpin the innate anti-viral responses of airway epithelial cells to RV and CoV. In Chapter Three, we present findings showing that the PI3K signalling pathway is not utilised in primary bronchial epithelial cells (pBECs) from healthy or COPD donors during rhinovirus infection in contrast to what has previously been reported for Influenza A infection. In Chapter Four, we established a CoV infection model in pBECs grown at air liquid interface, utilising two CoVs, 229E (an alpha CoV) and OC43 (a beta CoV). This model was used to demonstrate the unique replication kinetics, interferon responses and gene profiles of 229E and OC43 infection in Chapter Five. Chapter Six further investigates these differences in epithelium from COPD donors during infection to determine how these host epithelial responses impact chronic respiratory diseases. We have identified innate immune mechanisms that define different, clinically important respiratory viruses, identifying distinct host- and viral-strategies that determine the outcome of infection and disease.
- Subject
- coronavirus; 229E; OC43; rhinovirus; innate immune response; airway epithelium
- Identifier
- http://hdl.handle.net/1959.13/1388350
- Identifier
- uon:32746
- Rights
- Copyright 2018 Su-Ling Loo
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 16 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 679 KB | Adobe Acrobat PDF | View Details Download |