Date of Award

Fall 2012

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences (Molecular Virology and Immunology Program)

Supervisor

Karen L. Mossman

Co-Supervisor

Brian D. Lichty

Language

English

Committee Member

Ali A. Ashkar

Abstract

The transcription factor interferon (IFN) regulatory factor 3 (IRF-3) plays a central role in the innate immune response to viral stimulation. IRF-3 participates in both the type I IFN-dependent and -independent signalling pathways that result in the induction of an antiviral state. The work presented in this thesis characterizes the central role of IRF-3 in the IFN-independent response to virus particle entry. In addition, novel splice variants of human IRF-3 are identified and characterized, implying a role for splice-mediated regulation of IRF-3-mediated antiviral signalling. Finally, a role for reactive oxygen species in the activation of IRF-3 following virus particle entry is described, with virus particle entry inducing danger associated molecular patterns associated with IRF-3 activation and IFN-independent antiviral gene expression. Taken together, this thesis characterizes the role of IRF-3 in the innate antiviral signalling pathways activated following viral stimulation, and highlight the importance of danger-associated molecular patterns as important mediators of antiviral signalling.

McMaster University Library


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