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.
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.
Iordanov
M S
MS
Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97201, USA.
Wong
J
J
Bell
J C
JC
Magun
B E
BE
D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004686:Encephalomyocarditis virus / Q000235:genetics*; D004722:Endoribonucleases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins; D016899:Interferon-beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational; D012330:RNA, Double-Stranded / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014452:Ubiquitins / Q000378:metabolism; D019892:eIF-2 Kinase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D015850:Interleukin-6; D009097:Multienzyme Complexes; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D014452:Ubiquitins; D016899:Interferon-beta; D004247:DNA; D019892:eIF-2 Kinase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex