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PMID: 11113181 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Activation of NF-kappaB 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.

Molecular and cellular biology ·Vol. 21 ·No. 1 ·2001-01-00 ·Pages 61-72

Iordanov MS, Wong J, Bell JC, Magun BE

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-kappaB 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-kappaB by dsRNA. Here we present evidence that the dsRNA-induced NF-kappaB 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.

MeSH Terms
Active Transport, Cell Nucleus Animals Apoptosis Cell Line Cysteine Endopeptidases/metabolism DNA/genetics,metabolism DNA-Binding Proteins/metabolism Encephalomyocarditis virus/genetics Endoribonucleases/deficiency,genetics,metabolism Gene Deletion Gene Expression Regulation I-kappa B Proteins Interferon-beta/genetics Interleukin-6/genetics Mice Multienzyme Complexes/metabolism NF-kappa B/metabolism Phosphorylation Proteasome Endopeptidase Complex Protein Processing, Post-Translational RNA, Double-Stranded/metabolism RNA, Messenger/genetics,metabolism RNA, Viral/metabolism Tumor Necrosis Factor-alpha/genetics Ubiquitins/metabolism eIF-2 Kinase/deficiency,genetics,metabolism
Chemicals
DNA-Binding Proteins I kappa B beta protein I-kappa B Proteins Interleukin-6 Multienzyme Complexes NF-kappa B RNA, Double-Stranded RNA, Messenger RNA, Viral Tumor Necrosis Factor-alpha Ubiquitins Interferon-beta DNA eIF-2 Kinase Endoribonucleases 2-5A-dependent ribonuclease Cysteine Endopeptidases Proteasome Endopeptidase Complex
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Iordanov M S
Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97201, USA.
Wong J
Bell J C
Magun B E
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.1.61-72.2001
Published
2001-01-00
Pages
61-72
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC88780
Subset
IM
Grants
NCI NIH HHS · R01 CA039360 · United States
NIEHS NIH HHS · R01 ES008456 · United States
NCI NIH HHS · CA-39360 · United States
NIEHS NIH HHS · ES-08456 · United States
External Links
PubMed source DOI: 10.1128/MCB.21.1.61-72.2001 PMC Full Text View journal details
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