microRNAs (miRNAs) are a class of noncoding RNAs that regulate gene expression. This class of 18-25 nucleotide-long non-coding RNAs has been found to play critical roles in the modulation of a wide spectrum of cellular processes including immunity, development, and metabolism. They modulate their interactions by binding to the 3’ untranslated region of the target messenger RNA to mediate the repression of gene expression. Given their emerging critical roles in the regulation of biological processes, it is not surprising that miRNAs play a significant part in modulating host-virus interactions. Viruses are obligate parasites that hijack the host cellular machinery and processes to promote their life cycle and their propagation. Emerging evidence suggests that miRNAs add an extra regulatory layer to fine-tune viral pathogenesis. This offers novel opportunities not only to delineate the crosstalk between the host and the virus but also allows for the development of novel therapeutics and the identification of novel potential biomarkers of viral infection. Herein, we examine the roles of various miRNAs in the modulation of host-virus interactions. In this thesis, we identify a polycistronic miRNA cluster (miR-183, miR-96, and miR-182) to possess antiviral properties against RNA viruses by augmenting innate immune responses to viral infection. We as well identify miR-383 to possess novel antiviral potential against Dengue virus (DENV), through its targeting of PLA2G4A, a pro-viral host factor essential for the production of infectious particles. Finally, we examine miR-185’s role in the modulation of SARS-CoV-2 infection where we show that miR-185’s regulation of fatty acid and cholesterol metabolism suppresses the virus’s entry and propagation in lung and liver cells. Collectively, the findings in this thesis demonstrate the critical role that miRNAs play in the modulation of host-virus interaction through modifying the host’s cellular environment essential for the regulation of viral pathogenesis.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/44505 |
| Date | 13 January 2023 |
| Creators | Ahmed, Nadine |
| Contributors | Pezacki, John |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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