THE ROLE OF INTERFERON REGULATORY FACTOR 3 IN THE INNATE ANTIVIRAL RESPONSE

Abstract

<p>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.</p>