Show simple item record Kao, C. Cheng Ranjith-Kumar, C. T. Mukhopadhyay, Suchetana Zlotnick, Adam Valverde, Rodrigo A. Tragesser, Brady J. Bhardwaj, Kanchan Chen, Alice Yi, Guanghui Lai, Yvonne 2012-04-04T17:09:05Z 2012-04-04T17:09:05Z 2011-10
dc.identifier.citation Lai, Y., Yi, G., Chen, A., Bhardwaj, K., Valverde,R. A., Zlotnick, A., Mukhopadhyay, S., Ranjith-Kumar, C. T., and Kao, C. C. 2011. Viral double-strand RNA-binding proteins can enhance innate immune signaling by Toll-like Receptor 3. PLoS ONE 6(10): e25837. en
dc.description.abstract Toll-like Receptor 3 (TLR3) detects double-stranded (ds) RNAs to activate innate immune responses. While poly(I:C) is an excellent agonist for TLR3 in several cell lines and in human peripheral blood mononuclear cells, viral dsRNAs tend to be poor agonists, leading to the hypothesis that additional factor(s) are likely required to allow TLR3 to respond to viral dsRNAs. TLR3 signaling was examined in a lung epithelial cell line by quantifying cytokine production and in human embryonic kidney cells by quantifying luciferase reporter levels. Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells when added to the media along with either poly(I:C) or viral dsRNAs. The polymerase from the genotype 2a JFH-1 HCV was a poor enhancer of TLR3 signaling until it was mutated to favor a conformation that could bind better to a partially duplexed RNA. The 1b polymerase also co-localizes with TLR3 in endosomes. RNA-binding capsid proteins (CPs) from two positive-strand RNA viruses and the hepadenavirus hepatitis B virus (HBV) were also potent enhancers of TLR3 signaling by poly(I:C) or viral dsRNAs. A truncated version of the HBV CP that lacked an arginine-rich RNA-binding domain was unable to enhance TLR3 signaling. These results demonstrate that several viral RNA-binding proteins can enhance the dsRNA-dependent innate immune response initiated by TLR3. en
dc.description.sponsorship CCK acknowledges funding from National Institute of Allergy and Infectious Diseases grants RAI075015A, 1RO1AI073335 and 1RO1090280. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. en
dc.language.iso en_US en
dc.publisher PLoS en
dc.relation.isversionof doi:10.1371/journal.pone.0025837 en
dc.rights Copyright: 2011 Lai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en
dc.title Viral Double-Strand RNA-Binding Proteins Can Enhance Innate Immune Signaling by Toll-Like Receptor 3 en
dc.type Article en

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