- Title
- Rhinovirus diversity and replication in differentiated airway epithelial cells
- Creator
- Esneau, Camille
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2020
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Rhinovirus (RV) are amongst the most common respiratory viruses worldwide. They are the cause of most common cold illnesses and are also implicated in a wide range of more severe illnesses, notably chronic respiratory illnesses such as asthma, resulting in a significant clinical and economic burden. To this day, research has mainly revolved around the study of host responses to infection, and the impact of RV genetics on illness severity remains overlooked. This thesis aims to understand this diversity with a special focus on RV replication in the airway epithelium. In chapter 3, we report findings of a meta-analysis aimed at assessing RV diversity in relation to illness in already published clinical studies using typing. In this chapter, we highlighted differences in the frequency of detection of RV subtypes, suggesting that RV subtypes may not all have the same clinical relevance. Notably, RV-A12 and RV-A78 were identified in the majority of clinical studies, with the large number of cases and over several years. In contrast to these overall prevalent RVs, some RV subtypes, such as RVA89, were typed more frequently in studies using samples from hospitalised patients. In chapter 4, we characterised a panel of RV subtypes by investigating their replication in airway epithelial cells at air-liquid interface, and the corresponding gene and protein induction responsible for the establishment of an anti-viral state. We found that RV subtypes were diverse from each other in terms of their replication kinetics and distinct in the induction of epithelial innate immune responses. In particular, we report that the main RV subtypes used in our laboratory behaves as an outlier, exhibiting higher viral loads and stronger innate epithelial responses to infection than all other RV subtypes investigated. In chapter 5, our aim was to develop a reporter system which could be utilised to observe replication in epithelial cells using fluorescence microscopy. We report the use of two different approaches for this purpose: a recombinant RV expressing eGFP upon replication, and a two-step system through the development of a reporter cell line responding to infection with a tat expressing recombinant virus. These two attempts at developing a reporter system were unsuccessful. Taken together, this thesis presents evidence to suggest that there is great diversity amongst rhinovirus subtypes, reflected in distinct replication kinetics and the induction of varied anti viral host immune responses. Both the meta-analysis and in-vitro infection cell culture models utilised in this study demonstrate the importance of examining each RV subtype individually. This is particularly important in the search for anti-viral therapies against RVs.
- Subject
- Rhinovirus; meta analysis; replication; epithelial cells; reporter system
- Identifier
- http://hdl.handle.net/1959.13/1422288
- Identifier
- uon:37816
- Rights
- Copyright 2020 Camille Esneau
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 6 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 863 KB | Adobe Acrobat PDF | View Details Download |