About: 2′-O Methylation of the Viral mRNA Cap by West Nile Virus Evades Ifit1-Dependent and -Independent Mechanisms of Host Restriction In Vivo

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About: 2′-O Methylation of the Viral mRNA Cap by West Nile Virus Evades Ifit1-Dependent and -Independent Mechanisms of Host Restriction In Vivo Goto Sponge NotDistinct Permalink

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	2′-O Methylation of the Viral mRNA Cap by West Nile Virus Evades Ifit1-Dependent and -Independent Mechanisms of Host Restriction In Vivo
Creator	Gale, Michael Cho, Hyelim Diamond, Michael Gack, Michaela Klein, Robyn Sen, Ganes Szretter, Kristy Virgin, Herbert Daniels, Brian Gainey, Maria Yokoyama, Wayne
Source	Medline; PMC
abstract	Prior studies have shown that 2′-O methyltransferase activity of flaviviruses, coronaviruses, and poxviruses promotes viral evasion of Ifit1, an interferon-stimulated innate immune effector protein. Viruses lacking 2′-O methyltransferase activity exhibited attenuation in primary macrophages that was rescued in cells lacking Ifit1 gene expression. Here, we examined the role of Ifit1 in restricting pathogenesis in vivo of wild type WNV (WNV-WT) and a mutant in the NS5 gene (WNV-E218A) lacking 2′-O methylation of the 5′ viral RNA cap. While deletion of Ifit1 had marginal effects on WNV-WT pathogenesis, WNV-E218A showed increased replication in peripheral tissues of Ifit1 (−/−) mice after subcutaneous infection, yet this failed to correlate with enhanced infection in the brain or lethality. In comparison, WNV-E218A was virulent after intracranial infection as judged by increased infection in different regions of the central nervous system (CNS) and a greater than 16,000-fold decrease in LD(50) values in Ifit1 (−/−) compared to wild type mice. Ex vivo infection experiments revealed cell-type specific differences in the ability of an Ifit1 deficiency to complement the replication defect of WNV-E218A. In particular, WNV-E218A infection was impaired in both wild type and Ifit1 (−/−) brain microvascular endothelial cells, which are believed to participate in blood-brain barrier (BBB) regulation of virus entry into the CNS. A deficiency of Ifit1 also was associated with increased neuronal death in vivo, which was both cell-intrinsic and mediated by immunopathogenic CD8(+) T cells. Our results suggest that virulent strains of WNV have largely evaded the antiviral effects of Ifit1, and viral mutants lacking 2′-O methylation are controlled in vivo by Ifit1-dependent and -independent mechanisms in different cell types.
has issue date	2012-05-10(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1002698
bibo:pmid	22589727
has license	cc-by
sha1sum (hex)	c20b981bab1fda3ce4c37eaa63bab33cb4ba88db
schema:url	https://doi.org/10.1371/journal.ppat.1002698
resource representing a document's title	2′-O Methylation of the Viral mRNA Cap by West Nile Virus Evades Ifit1-Dependent and -Independent Mechanisms of Host Restriction In Vivo
has PubMed Central identifier	PMC3349756
has PubMed identifier	22589727
schema:publication	PLoS Pathog
resource representing a document's body	covid:c20b981bab1fda3ce4c37eaa63bab33cb4ba88db#body_text
is schema:about of	named entity 'virus' named entity 'effector protein' named entity 'antiviral' named entity 'tissues' named entity 'mRNA' named entity 'values' named entity 'infection' named entity 'replication' named entity 'mutant' named entity 'lethality' named entity 'central nervous system (CNS)' named entity 'macrophages' named entity 'flaviviruses' named entity 'infection' named entity 'poxviruses' named entity 'pathogenesis' named entity 'neuronal death' named entity 'effector protein' named entity 'WNV' named entity 'Viruses' named entity 'infection' named entity 'WNV' named entity 'mice' named entity 'WNV' named entity 'Ifit1' named entity 'virus entry' named entity 'gene expression' named entity 'BBB' named entity 'WNV' named entity 'Ifit1' named entity 'central nervous' named entity 'Ifit1' named entity 'infection' named entity 'Ifit1' named entity 'mRNA' named entity 'West Nile Virus' named entity 'greater' named entity 'Prior' named entity 'serum' named entity 'viral RNA' named entity 'inflammatory cell' named entity 'Percoll' named entity 'signaling pathways' named entity 'RNA' named entity 'cell-type' named entity 'WNV' named entity 'neurons' named entity 'cerebellum' named entity 'macrophages' named entity 'MHV' named entity 'CNS' named entity 'phenotype' named entity 'subcutaneously' named entity 'primer' named entity 'viral burden' named entity 'Ifit1' named entity 'wild type' named entity 'infection' named entity 'mice' named entity 'mice' named entity 'mice' named entity 'pathogenesis' named entity 'Sindbis' named entity 'frozen section' named entity 'Ifit1' named entity 'RNA' named entity 'National Institutes of Health' named entity 'pathogenesis' named entity 'endothelial cells' named entity 'neurons' named entity 'TUNEL'

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