About: Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice

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About: Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice Goto Sponge NotDistinct Permalink

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	Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice
Creator	Baric, Ralph Gralinski, Lisa Schäfer, Alexandra Beall, Anne Kocher, Jacob Plante, Jessica Menachery, Vineet Totura, Allison Ferris, Martin Morgan, Andrew Harrison-Shostak, D Pardo-Manuel De Villena, Fernando
source	Medline; PMC
abstract	Host genetic variation is known to contribute to differential pathogenesis following infection. Mouse models allow direct assessment of host genetic factors responsible for susceptibility to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). Based on an assessment of early stage lines from the Collaborative Cross mouse multi-parent population, we identified two lines showing highly divergent susceptibilities to SARS-CoV: the resistant CC003/Unc and the susceptible CC053/Unc. We generated 264 F2 mice between these strains, and infected them with SARS-CoV. Weight loss, pulmonary hemorrhage, and viral load were all highly correlated disease phenotypes. We identified a quantitative trait locus of major effect on chromosome 18 (27.1–58.6 Mb) which affected weight loss, viral titer and hemorrhage. Additionally, each of these three phenotypes had distinct quantitative trait loci [Chr 9 (weight loss), Chrs 7 and 12 (virus titer), and Chr 15 (hemorrhage)]. We identified Ticam2, an adaptor protein in the TLR signaling pathways, as a candidate driving differential disease at the Chr 18 locus. Ticam2(−/−) mice were highly susceptible to SARS-CoV infection, exhibiting increased weight loss and more pulmonary hemorrhage than control mice. These results indicate a critical role for Ticam2 in SARS-CoV disease, and highlight the importance of host genetic variation in disease responses.
has issue date	2017-06-05(xsd:dateTime)
bibo:doi	10.1534/g3.117.041434
bibo:pmid	28592648
has license	cc-by
sha1sum (hex)	6d5c9139359f0be11be696bec88268a4f1cf7131
schema:url	https://doi.org/10.1534/g3.117.041434
resource representing a document's title	Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice
has PubMed Central identifier	PMC5473747
has PubMed identifier	28592648
schema:publication	G3 (Bethesda)
resource representing a document's body	covid:6d5c9139359f0be11be696bec88268a4f1cf7131#body_text
is schema:about of	named entity 'infected' named entity 'hemorrhage' named entity 'stage lines' named entity 'highlight' named entity 'host' named entity 'control' named entity 'SUSCEPTIBLE' named entity 'VIRAL LOAD' named entity 'EARLY STAGE' named entity 'DRIVING' named entity 'PROTEIN ' named entity 'ADAPTOR PROTEIN' named entity 'KNOWN' named entity 'SIGNALING PATHWAYS' named entity 'HOST' named entity 'COLLABORATIVE' covid:arg/6d5c9139359f0be11be696bec88268a4f1cf7131 named entity 'EXHIBITING' named entity 'PARENT' named entity 'STRAINS' named entity 'CONTRIBUTE ' named entity 'PROTEIN ' named entity 'MOUSE MULTI' named entity 'CORRELATED' named entity 'CHROMOSOME 18' named entity 'AFFECTED' named entity 'SARS' named entity 'TICAM2' named entity 'SARS-COV INFECTION' named entity 'MAJOR' named entity 'CANDIDATE' named entity 'CROSS' named entity 'BASED' named entity 'TITER' named entity 'TOLL-LIKE RECEPTOR' named entity 'MICE' named entity 'ALLELIC VARIATION' named entity 'CHRS' named entity 'INFECTION' named entity 'LOCUS' named entity 'QUANTITATIVE TRAIT LOCI' named entity 'SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS' named entity 'EFFECT' named entity 'HIGHLY' named entity 'POPULATION' named entity 'IDENTIFIED' named entity 'ROLE' named entity 'CRITICAL' named entity 'LOSS' named entity 'ADAPTOR PROTEIN' named entity 'FOLLOWING' named entity 'THESE' named entity 'GENERATED' named entity 'RESISTANT' named entity 'LINES' named entity 'SARS-COV' named entity 'TICAM2' named entity 'GENETIC FACTORS' named entity 'INFECTED' named entity 'SUSCEPTIBILITY' named entity 'PATHOGENESIS' named entity 'RESULTS' named entity 'MOUSE MODELS' named entity 'GENETIC VARIATION' named entity 'PHENOTYPES' named entity 'CHR' named entity 'QUANTITATIVE TRAIT LOCUS' named entity 'ASSESSMENT' named entity 'INCREASED WEIGHT' named entity 'RESPONSES'

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