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Journal of Virology, May 2009, p. 4013-4022, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02069-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Differential Modification of Interferon Regulatory Factor 3 following Virus Particle Entry{triangledown} ,{dagger}

Ryan S. Noyce,1,{ddagger} Susan E. Collins,2 and Karen L. Mossman1,2*

Department of Biochemistry and Biomedical Sciences,1 Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, Michael DeGroote Centre for Learning and Discovery, McMaster University, Hamilton, Ontario, Canada2

Received 2 October 2008/ Accepted 2 February 2009

Viral infection elicits the activation of numerous cellular signal transduction pathways, leading to the induction of both innate and adaptive immune responses in the host. In particular, interferon regulatory factor 3 (IRF3) has been shown to be essential for the induction of an antiviral response. Current models suggest that virus replication causes phosphorylation of C-terminal serine and threonine residues on IRF3, leading to its dimerization and translocation to the nucleus, where it activates interferon. Upon entry of replication-deficient Newcastle disease virus (NDV) particles, however, we failed to detect IRF3 dimerization or hyperphosphorylation, despite robust interferon-stimulated gene (ISG) and antiviral state induction and confirmation by small interfering RNA knockdown that IRF3 is essential for this response. To further compare the effects of various viruses and their replication status on IRF3 activation and to determine the minimal posttranslational modification required for IRF3 activation, two-dimensional gel electrophoresis and native polyacrylamide gel electrophoresis were employed. However, we failed to identify a minimal posttranslational modification of IRF3 that correlated with downstream biological activity, and the extent of posttranslational modification observed on IRF3 did not correlate with the degree of subsequent ISG induction. Thus, current techniques used to detect IRF3 activation are insufficient to infer its role in mediating downstream biological response induction and should be utilized with caution.

* Corresponding author. Mailing address: Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, Michael DeGroote Centre for Learning and Discovery, Room 5026, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. Phone: (905) 525-9140, ext. 23542. Fax: (905) 522-6750. E-mail: mossk{at}mcmaster.ca

{triangledown} Published ahead of print on 11 February 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} Present address: Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.

Journal of Virology, May 2009, p. 4013-4022, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02069-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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