About: Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity
Creator	Rodriguez, Moses Ross, Susan Warrington, Arthur Poeschla, Eric Rinkoski, Tommy Bieber, Allan Matchett, William Morrison, James Painter, Meghan Papke, Louisa Turkowski, Kari Watzlawik, Jens Zoecklein, Laurie
topic	covid:59b1eae28c32b9852ebe3707da0e9c469e9ea2dc#this
source	Medline; PMC
abstract	For many emerging and re-emerging infectious diseases, definitive solutions via sterilizing adaptive immunity may require years or decades to develop, if they are even possible. The innate immune system offers alternative mechanisms that do not require antigen-specific recognition or a priori knowledge of the causative agent. However, it is unclear whether effective stable innate immune system activation can be achieved without triggering harmful autoimmunity or other chronic inflammatory sequelae. Here, we show that transgenic expression of a picornavirus RNA-dependent RNA polymerase (RdRP), in the absence of other viral proteins, can profoundly reconfigure mammalian innate antiviral immunity by exposing the normally membrane-sequestered RdRP activity to sustained innate immune detection. RdRP-transgenic mice have life-long, quantitatively dramatic upregulation of 80 interferon-stimulated genes (ISGs) and show profound resistance to normally lethal viral challenge. Multiple crosses with defined knockout mice (Rag1, Mda5, Mavs, Ifnar1, Ifngr1, and Tlr3) established that the mechanism operates via MDA5 and MAVS and is fully independent of the adaptive immune system. Human cell models recapitulated the key features with striking fidelity, with the RdRP inducing an analogous ISG network and a strict block to HIV-1 infection. This RdRP-mediated antiviral mechanism does not depend on secondary structure within the RdRP mRNA but operates at the protein level and requires RdRP catalysis. Importantly, despite lifelong massive ISG elevations, RdRP mice are entirely healthy, with normal longevity. Our data reveal that a powerfully augmented MDA5-mediated activation state can be a well-tolerated mammalian innate immune system configuration. These results provide a foundation for augmenting innate immunity to achieve broad-spectrum antiviral protection.
has issue date	2015-12-03(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1005311
bibo:pmid	26633895
has license	cc-by
sha1sum (hex)	59b1eae28c32b9852ebe3707da0e9c469e9ea2dc
schema:url	https://doi.org/10.1371/journal.ppat.1005311
resource representing a document's title	Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity
has PubMed Central identifier	PMC4669089
has PubMed identifier	26633895
schema:publication	PLoS Pathog
resource representing a document's body	covid:59b1eae28c32b9852ebe3707da0e9c469e9ea2dc#body_text
is http://vocab.deri.ie/void#inDataset of	proxy:http/ns.inria.fr/covid19/59b1eae28c32b9852ebe3707da0e9c469e9ea2dc
is schema:about of	named entity 'analogous' named entity 'Human' named entity 'immunity' named entity 'secondary structure' named entity 'This' named entity 'The' named entity 'antiviral' named entity 'knockout mice' named entity 'inducing' named entity 'Rag1' named entity 'upregulation' named entity 'immunity' named entity 'RdRP' named entity 'data' named entity 'agent' named entity 'mRNA' named entity 'Tlr3' named entity 'Here' named entity 'striking' named entity 'triggering' named entity 'Our' named entity 'quantitatively' named entity 'innate immune system' named entity 'longevity' named entity 'catalysis' named entity 'broad-spectrum' named entity 'sterilizing' named entity 'Stable' named entity 'autoimmunity' named entity 'antiviral' named entity 'Ifnar1' named entity 'protein' named entity 'causative agent' named entity 'innate immunity' named entity 'ISG' named entity 'transgenic mice' named entity 'chronic inflammatory' named entity 'Antiviral' named entity 'RdRP' named entity 'infectious diseases' named entity 'chronic' named entity 'antiviral' named entity 'mice' named entity 'PDF' named entity 'chronic inflammatory' named entity 'cerebrum' named entity 'antiviral' named entity 'influenza' named entity 'Gapdh' named entity 'RT-PCR' named entity 'Affymetrix' named entity 'Ebola' named entity 'biotinylated' named entity 'RdRP' named entity 'Gapdh' named entity 'poliovirus' named entity 'genotype' named entity 'IFNα' named entity 'RNA' named entity 'THP-1' named entity 'transfected' named entity 'viral infection' named entity 'mice' named entity 'multicellular' named entity 'cytokine' named entity 'transgenic' named entity 'Hungary'

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