The regulation of human airway epithelial expression of viperin by human rhinovirus

Human rhinovirus (HRV) is a major trigger of exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Cigarette smoke is the primary cause of COPD, and 25% of asthmatics smoke. Asthmatic subjects who smoke have more severe disease. Smokers also have more frequent and severe viral infections. Viperin is a novel antiviral molecule that is induced in airway epithelial cells following HRV infection and that inhibits replication of HRV in these cells. We investigated the mechanisms of HRV-induced epithelial viperin expression, and the effect of cigarette smoke extract (CSE) on this expression. We show that viperin expression is transcriptionally regulated and is dependent on induction and DNA binding of interferon regulatory factor 1 (IRF-1). We showed that CSE inhibits HRV-induced viperin mRNA and protein expression but that CSE does not alter HRV-induced promoter activation, raising the possibility that CSE-mediated inhibition of viperin induction is due to epigenetic regulation.

Name thesis:degree_name

Master of Science (MSc)

Discipline thesis:degree_discipline

Cardiovascular & Respiratory Sciences

Grantor dc:publisher.institution

Graduate Studies

Year dc:date.issued

2012

Author dc:creator

• Pelikan, Jonathan Benjamin

Advisor dc:contributor.advisor

• Proud, David

• Health Sciences

Statement dc:rights

• University 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.

Language dc:language.iso

eng

DOI

http://dx.doi.org/10.11575/PRISM/28289

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:11023/199