The regulation and function of viperin during rhinovirus infection

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dc.contributor.advisorProud, David
dc.contributor.advisorLeigh, Richard
dc.contributor.authorLove, Michelle
dc.contributor.committeememberGrandvaux, Nathalie
dc.contributor.committeememberJenne, Craig
dc.contributor.committeememberHirota, Simon
dc.contributor.committeememberYipp, Bryan
dc.date2023-02
dc.date.accessioned2022-12-22T21:22:34Z
dc.date.available2022-12-22T21:22:34Z
dc.date.issued2022-12-19
dc.description.abstractThe airway epithelium is the primary site of rhinovirus replication and plays a pivotal role in orchestrating innate immune responses to respiratory viruses, including rhinovirus. Interfacing with inhaled material in the airway lumen, the airway epithelium experiences continuous onslaught from respiratory pathogens. To combat viral infection, cells of the airway epithelium express a range of pattern recognition receptors capable of recognizing diverse viral ligands. Detection of an infectious virus by one of these receptors rapidly upregulates an array of effector molecules, including pro-inflammatory cytokines, interferons and interferon stimulated genes. Viperin is one of the most highly upregulated interferon stimulated genes in rhinovirus infected airway epithelial cells. Viperin expression during viral infection has long been associated with direct antiviral effects across diverse viral infection and cell models, including in rhinovirus infected airway epithelial cells. Despite the long-standing knowledge that viperin expression helps to impedes rhinovirus replication in the airway epithelium, little is known about how it is upregulated in response to rhinoviruses or how viperin proceeds to impact airway epithelial cell biology during infection. In addition to confirming previously published findings demonstrating that viperin is induced in rhinovirus infected primary human airway epithelial cells and is dependent on viral replication, we also demonstrated induction of viperin in airway epithelial cells by interferons. We also highlight the importance of the type III interferon IL-29 as a potent inducer of viperin in the airway epithelium. Finally based on our findings we propose a novel feedback loop, according to this model detection of rhinoviruses by the cytosolic dsRNA receptor melanoma differentiation-associated protein 5 (MDA5), or IL-29 signalling, promotes IRF-1 mediated viperin transcription. Viperin then establishes a protein-protein interaction with MDA5 which results in enhanced MDA5 stability in RV infected cells. This leads to enhanced signalling through MDA5, as measured by increased CXCL10 gene expression and protein secretion. As we have also demonstrated that MDA5 signalling is involved in promoting viperin expression in response to RV we hypothesize that stabilization of MDA5 by viperin may also serves to amplify viperin production during infection.en_US
dc.identifier.citationLove, M. (2022). The regulation and function of viperin during rhinovirus infection (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.urihttp://hdl.handle.net/1880/115625
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/40559
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectviperinen_US
dc.subjectairway epitheliumen_US
dc.subjectrhinovirusen_US
dc.subjectinnate immunityen_US
dc.subject.classificationBiology--Cellen_US
dc.subject.classificationBiology--Molecularen_US
dc.subject.classificationVirologyen_US
dc.subject.classificationImmunologyen_US
dc.titleThe regulation and function of viperin during rhinovirus infectionen_US
dc.typedoctoral thesisen_US
thesis.degree.disciplineMedicine – Cardiovascular/Respiratory Scienceen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameDoctor of Philosophy (PhD)en_US
ucalgary.item.requestcopytrueen_US
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