About: Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation

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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
has title	Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation
Creator	Perlman, Stanley Palese, Peter Baric, Ralph Weiss, Susan Sims, Amy Yount, Boyd Elliott, Ruth Li, Yize Li, Y Bk, Jha Goldstein, Stephen Jha, Babal Jm, Thornbrough Silverman, Robert Thornbrough, Joshua Ac, Sims Rs, Baric Rh, Silverman Sa, Goldstein
Source	Medline; PMC
abstract	Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. Evasion of host innate immunity through interferon (IFN) antagonism is a critical component of viral pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L cleaves viral and host single-stranded RNA (ssRNA), which leads to translational arrest and subsequent cell death, preventing viral replication and spread. Here we report that MERS-CoV, a lineage C Betacoronavirus, and related bat CoV NS4b accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase L by enzymatically degrading 2′,5′-oligoadenylate (2-5A), activators of RNase L. This is a novel function for NS4b, which has previously been reported to antagonize IFN signaling. NS4b proteins are distinct from lineage A Betacoronavirus PDEs and rotavirus gene-encoded PDEs, in having an amino-terminal nuclear localization signal (NLS) and are localized mostly to the nucleus. However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient to prevent activation of RNase L. Finally, this is the first report of an RNase L antagonist expressed by a human or bat coronavirus and provides a specific mechanism by which this occurs. Our findings provide a potential mechanism for evasion of innate immunity by MERS-CoV while also identifying a potential target for therapeutic intervention.
has issue date	2016-03-29(xsd:dateTime)
bibo:doi	10.1128/mbio.00258-16
bibo:pmid	27025250
has license	cc-by
sha1sum (hex)	21d0dff90077800702fb5a6502246e9d512b6fe8
schema:url	https://doi.org/10.1128/mbio.00258-16
resource representing a document's title	Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation
has PubMed Central identifier	PMC4817253
has PubMed identifier	27025250
schema:publication	mBio
resource representing a document's body	covid:21d0dff90077800702fb5a6502246e9d512b6fe8#body_text
is schema:about of	named entity 'mechanism' named entity 'interferon' named entity 'antagonism' named entity 'Like' named entity 'MERS-CoV' named entity 'Middle East respiratory syndrome' named entity 'viral pathogenesis' named entity 'PROTEIN ' named entity 'PHOSPHODIESTERASE' named entity 'OLIGOADENYLATE' named entity 'LEADS' named entity 'LIKE' named entity 'HERE' named entity 'ACTIVATION' named entity 'FINDINGS' named entity 'THERAPEUTIC INTERVENTION' named entity 'IFN' named entity 'SUBSEQUENT' named entity 'CORONAVIRUSES' named entity 'SPREAD' named entity 'HUMAN CORONAVIRUS' named entity 'LINEAGE' named entity 'LOCALIZED' named entity 'BUT' named entity 'RELATED' named entity 'VIRAL PATHOGENESIS' named entity 'REPORTED' named entity 'SYNTHETASE' named entity 'BAT CORONAVIRUS' named entity 'TARGET' named entity 'VIRAL' named entity 'PROVIDE' named entity 'VIRAL REPLICATION' named entity 'EXPRESSED' named entity 'ENCODE' named entity '282' named entity 'ENCODED' named entity 'NS4B' named entity 'PROTEIN ' named entity 'EXPRESSION LEVEL' named entity 'CARRIES' named entity 'VIRAL AND' named entity '2C5' named entity 'SINGLE-STRANDED RNA' named entity 'SENSING' named entity 'INNATE IMMUNITY' named entity 'BETACORONAVIRUS' named entity 'IS A' named entity 'ACTIVATES' named entity 'GENE' named entity 'PATHOGENESIS' named entity 'OAS' named entity 'POTENTIAL' named entity 'TERMINAL' named entity 'PATHOGENIC' named entity 'NS4B PROTEIN' named entity 'HUMAN' named entity 'HIGHLY' named entity 'COMPONENT' named entity 'HOST' named entity 'CRITICAL' named entity 'MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS' named entity 'GENOME'

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