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Mol. Cell. Biol. 21 (1): 61-72

Copyright © 2001 by the American Society for Microbiology. All rights reserved.

Activation of NF-{kappa}B by Double-Stranded RNA (dsRNA) in the Absence of Protein Kinase R and RNase L Demonstrates the Existence of Two Separate dsRNA-Triggered Antiviral Programs

Mihail S. Iordanov,1 John Wong,1 John C. Bell,2,3, and Bruce E. Magun1,*

Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97201,1 and Ottawa Regional Cancer Center Research Laboratories, Ottawa, Ontario K1H 8L6,2 and Department of Biochemistry, University of Ottawa, Ottawa, Ontario K1H 8M5,3 Canada

Received for publication 27 June 2000. Revision received 8 August 2000. Accepted for publication 22 September 2000.

Abstract: Double-stranded RNA (dsRNA) of viral origin triggers two programs of the innate immunity in virus-infected cells. One is intended to decrease the rate of host cell protein synthesis and thus to prevent viral replication. This program is mediated by protein kinase R (PKR) and by RNase L and contributes, eventually, to the self-elimination of the infected cell via apoptosis. The second program is responsible for the production of antiviral (type I) interferons and other alarmone cytokines and serves the purpose of preparing naive cells for the viral invasion. This second program requires the survival of the infected cell and depends on the expression of antiapoptotic genes through the activation of the NF-{kappa}B transcription factor. The second program therefore relies on ongoing transcription and translation. It has been proposed that PKR plays an essential role in the activation of NF-{kappa}B by dsRNA. Here we present evidence that the dsRNA-induced NF-{kappa}B activity and the expression of beta interferon and inflammatory cytokines do not require either PKR or RNase L. Our results indicate, therefore, that the two dsRNA-activated programs are separate and can function independently of each other.

* Corresponding author. Mailing address: Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, OR 97201. Phone: (503) 494-7811. Fax: (503) 494-4253. E-mail:magunb{at}OHSU.edu.

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