About: The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection

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About: The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection 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	The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection
Creator	Zhao, Jincun Perlman, Stanley Fett, Craig Athmer, Jeremiah Channappanavar, Rudragouda Ahel, Ivan Jankevicius, Gytis Meyerholz, David Fehr, Anthony
source	Medline; PMC
abstract	ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.
has issue date	2016-12-13(xsd:dateTime)
bibo:doi	10.1128/mbio.01721-16
bibo:pmid	27965448
has license	cc-by
sha1sum (hex)	788295abb7003fc90fdadb54283b664724c83b33
schema:url	https://doi.org/10.1128/mbio.01721-16
resource representing a document's title	The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection
has PubMed Central identifier	PMC5156301
has PubMed identifier	27965448
schema:publication	mBio
resource representing a document's body	covid:788295abb7003fc90fdadb54283b664724c83b33#body_text
is schema:about of	named entity 'members' named entity 'function' named entity 'Innate' named entity 'RIBOSE' named entity 'CONTAIN' named entity 'MUTATIONS' named entity 'SUPPRESSES' named entity 'HIGHLY' named entity 'ADP' named entity 'PROTEIN 3' named entity '27S' named entity 'INFECTION' named entity 'IDENTIFIED' named entity 'MEMBERS' named entity 'CORONAVIRUS INFECTION' named entity 'GREATLY' named entity 'INNATE IMMUNE RESPONSE' named entity 'CORONAVIRUS' named entity 'SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS' named entity 'SUBFAMILY' named entity 'REDUCED' named entity 'COVALENTLY ATTACHED' named entity 'CORONAVIRINAE' named entity 'ANTIVIRAL' named entity 'CONSERVED' named entity 'ADP-RIBOSYLATION' named entity 'PROTEIN ' named entity 'REMOVE' named entity 'FUNCTION' named entity 'A COMMON' named entity 'TARGETS' named entity 'POSTTRANSLATIONAL MODIFICATION' named entity 'SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS' named entity 'STRAINS' named entity 'IN VITRO' named entity 'MAY HAVE' named entity 'NSP3' named entity 'INNATE IMMUNITY' named entity 'CONSERVED' named entity 'CREATED' named entity 'UNKNOWN' named entity 'THESE' named entity 'VIRULENCE' named entity 'PROTEINS' named entity 'ITS' named entity 'ACTIVITY' named entity 'IMPACT' named entity 'RECOMBINANT' named entity 'IS A' named entity 'POSITIVE-SENSE RNA VIRUSES' named entity 'TO REGULATE' named entity 'PROPERTIES' covid:arg/788295abb7003fc90fdadb54283b664724c83b33 named entity 'conserved' named entity 'recombinant' named entity 'protein' named entity 'highly' named entity 'covalently' named entity 'Coronavirinae' named entity 'targets' named entity 'severe acute respiratory syndrome coronavirus' named entity 'mutations' named entity 'highly conserved' named entity 'ADP-ribosylation' named entity 'Coronavirinae' named entity 'posttranslational modification' named entity 'macrodomain' named entity 'recombinant' named entity 'antiviral' named entity 'covalently' named entity 'Severe Acute Respiratory Syndrome Coronavirus' named entity 'Innate Immune Response' named entity 'mice'

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