About: The PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Is a Determinant of Viral Pathogenesis

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About: The PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Is a Determinant of Viral Pathogenesis 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	The PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Is a Determinant of Viral Pathogenesis
Creator	Dediego, M Jimenez-Guardeñ O, J Nieto-Torres, J Regla-Nava, J Fernandez-Delgado, R
Source	Medline; PMC
abstract	A recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major determinant of virulence. Elimination of SARS-CoV E protein PBM by using reverse genetics caused a reduction in the deleterious exacerbation of the immune response triggered during infection with the parental virus and virus attenuation. Cellular protein syntenin was identified to bind the E protein PBM during SARS-CoV infection by using three complementary strategies, yeast two-hybrid, reciprocal coimmunoprecipitation and confocal microscopy assays. Syntenin redistributed from the nucleus to the cell cytoplasm during infection with viruses containing the E protein PBM, activating p38 MAPK and leading to the overexpression of inflammatory cytokines. Silencing of syntenin using siRNAs led to a decrease in p38 MAPK activation in SARS-CoV infected cells, further reinforcing their functional relationship. Active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM as compared with the parental virus, leading to a decreased expression of inflammatory cytokines and to virus attenuation. Interestingly, administration of a p38 MAPK inhibitor led to an increase in mice survival after infection with SARS-CoV, confirming the relevance of this pathway in SARS-CoV virulence. Therefore, the E protein PBM is a virulence domain that activates immunopathology most likely by using syntenin as a mediator of p38 MAPK induced inflammation.
has issue date	2014-08-14(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1004320
bibo:pmid	25122212
has license	cc-by
sha1sum (hex)	7c36bbbb2505c7eefacad040c39bd5b167969ad2
schema:url	https://doi.org/10.1371/journal.ppat.1004320
resource representing a document's title	The PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Is a Determinant of Viral Pathogenesis
has PubMed Central identifier	PMC4133396
has PubMed identifier	25122212
schema:publication	PLoS Pathog
resource representing a document's body	covid:7c36bbbb2505c7eefacad040c39bd5b167969ad2#body_text
is schema:about of	named entity 'PROTEIN ' covid:arg/7c36bbbb2505c7eefacad040c39bd5b167969ad2 named entity 'COMPARED' named entity 'SYNTENIN' named entity 'LACKING' named entity 'USING' named entity 'CELLS' named entity 'ACTIVE' named entity 'IS A' named entity 'CONFIRMING' named entity 'SURVIVAL' named entity 'FUNCTIONAL RELATIONSHIP' named entity 'PARENTAL' named entity 'RECIPROCAL' named entity 'LUNGS' named entity 'MICE' named entity 'HERE' named entity 'DETERMINANT' named entity 'ACTIVATES' named entity 'BINDING' named entity 'RELEVANCE' named entity 'MEDIATOR' named entity 'IMMUNOPATHOLOGY' named entity 'MAPK ACTIVATION' named entity 'YEAST TWO-HYBRID' named entity 'INDUCED' named entity 'IDENTIFIED' named entity 'PROTEIN-PROTEIN INTERACTIONS' named entity 'INFECTED' named entity 'COIMMUNOPRECIPITATION' named entity 'SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS' named entity 'CONFOCAL MICROSCOPY' named entity 'LEADING' named entity 'CELLULAR' named entity 'INCREASE' named entity 'SIRNAS' named entity 'SARS-COV' named entity 'REVERSE GENETICS' named entity 'P38 MAPK' named entity 'MOST LIKELY' named entity 'EXACERBATION' named entity 'DECREASED EXPRESSION' named entity 'PATHWAY' named entity 'REDUCTION' named entity 'A MAJOR' named entity 'ACTIVATING' named entity 'CAUSED' named entity 'CONTAINING' named entity 'TRIGGERED' named entity 'DECREASE' named entity 'RECOMBINANT' named entity 'NUCLEUS' named entity 'ENVELOPE' named entity 'COVS' named entity 'STRATEGIES' named entity 'MOTIF' named entity 'INFLAMMATORY' named entity 'CYTOPLASM' named entity 'LED' named entity 'THEIR' named entity 'DETERMINANT' named entity 'VIRUSES' named entity 'VIRUS' named entity 'BINDING' named entity 'PDZ' named entity 'IS A' named entity 'SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS' named entity 'PBM' named entity 'THE CELL' named entity 'SARS' named entity 'PDZ' named entity 'SARS-COV INFECTION' named entity 'MAPK INHIBITOR' named entity 'E PROTEIN' named entity 'ELIMINATION' named entity 'INFLAMMATION' named entity 'PROTEIN '

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