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Journal of Virology, October 2007, p. 11148-11158, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.00446-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

West Nile Virus-Induced Interferon Production Is Mediated by the Double-Stranded RNA-Dependent Protein Kinase PKR{triangledown} ,{dagger}

Felicia D. Gilfoy1 and Peter W. Mason1,2,3*

Departments of Pathology,1 Microbiology and Immunology,2 The Sealy Center for Vaccine Development, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 775553

Received 1 March 2007/ Accepted 25 July 2007

Cells carry a variety of molecules, referred to as pathogen recognition receptors (PRRs), which are able to sense invading pathogens. Interaction of PRRs with viral compounds instigates a signaling pathway(s), resulting in the activation of genes, including those for type I interferon (IFN), which are critical for an effective antiviral response. Here we demonstrate that the double-stranded RNA (dsRNA)-dependent protein kinase PKR, which has been shown to function as a PRR in cells treated with the dsRNA mimetic poly(I:C), serves as a PRR in West Nile virus (WNV)-infected cells. Evidence for PKR's role as a PRR was obtained from both human and murine cells. Using mouse embryonic fibroblasts (MEFs), we demonstrated that PKR gene knockout, posttranscriptional gene silencing of PKR mRNA using small interfering RNA (siRNA), and chemical inhibition of PKR function all interfered with IFN synthesis following WNV infection. In three different human cell lines, siRNA knockdown and chemical inhibition of PKR blocked WNV-induced IFN synthesis. Using the same approaches, we demonstrated that PKR was not necessary for Sendai virus-induced IFN synthesis, suggesting that PKR is particularly important for recognition of WNV infection. Taken together, our data suggest that PKR could serve as a PRR for recognition of WNV infection.

* Corresponding author. Mailing address: The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0436. Phone: (409) 747-8143. Fax: (409) 747-8150. E-mail: pwmason{at}utmb.edu

{triangledown} Published ahead of print on 8 August 2007.

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

Journal of Virology, October 2007, p. 11148-11158, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.00446-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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