About: Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis

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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	Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis
Creator	Baric, Ralph Gralinski, Lisa Sims, Amy Yount, Boyd Dinnon, Kenneth Debbink, Kari Menachery, Vineet Mitchell, Hugh Cockrell, Adam Graham, Rachel Leist, Sarah Mcanarney, Eileen Stratton, Kelly Waters, Katrina
Source	Medline; PMC
abstract	Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2′O-methyltransferase (2′O-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis. While the absence of 2′O-MTase activity had only a marginal impact on propagation and replication in Vero cells, dNSP16 mutant MERS-CoV demonstrated significant attenuation relative to the control both in primary human airway cell cultures and in vivo. Further examination indicated that dNSP16 mutant MERS-CoV had a type I interferon (IFN)-based attenuation and was partially restored in the absence of molecules of IFN-induced proteins with tetratricopeptide repeats. Importantly, the robust attenuation permitted the use of dNSP16 mutant MERS-CoV as a live attenuated vaccine platform protecting from a challenge with a mouse-adapted MERS-CoV strain. These studies demonstrate the importance of the conserved 2′O-MTase activity for CoV pathogenesis and highlight NSP16 as a conserved universal target for rapid live attenuated vaccine design in an expanding CoV outbreak setting. IMPORTANCE Coronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that effectively targets the highly conserved 2′O-MTase activity of CoVs for attenuation. With clear understanding of the IFN/IFIT (IFN-induced proteins with tetratricopeptide repeats)-based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform, as well as therapeutic development for both current and future emergent CoV strains. Importantly, other approaches targeting other conserved pan-CoV functions have not yet proven effective against MERS-CoV, illustrating the broad applicability of targeting viral 2′O-MTase function across CoVs.
has issue date	2017-11-15(xsd:dateTime)
bibo:doi	10.1128/msphere.00346-17
bibo:pmid	29152578
has license	cc-by
sha1sum (hex)	28a98145eda693bae14b52abfc3d37ced6c5fd90
schema:url	https://doi.org/10.1128/msphere.00346-17
resource representing a document's title	Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis
has PubMed Central identifier	PMC5687918
has PubMed identifier	29152578
schema:publication	mSphere
resource representing a document's body	covid:28a98145eda693bae14b52abfc3d37ced6c5fd90#body_text
is schema:about of	named entity 'INTERFERON ' named entity 'emergence' named entity 'critical' named entity 'therapeutic' named entity 'mutant' named entity 'conserved' named entity 'conserved' named entity 'MERS-CoV' named entity 'partially' named entity 'PROTEIN ' named entity 'RESISTANCE' named entity 'PROTEINS' named entity 'A MOUSE' named entity 'CURRENT' named entity 'PUBLIC HEALTH' named entity 'TARGET' covid:arg/28a98145eda693bae14b52abfc3d37ced6c5fd90 named entity 'CLEAR' named entity 'DELTA' named entity 'INDICATED' named entity 'DEVELOPMENT' named entity 'MTASE' named entity 'BROAD' named entity 'TARGETS' named entity 'CORONAVIRUS' named entity 'THERAPEUTIC' named entity 'SEVERE ACUTE RESPIRATORY SYNDROME' named entity 'VIRAL' named entity 'APPROACH' named entity 'PROVIDE' named entity 'RAPID' named entity 'PROTEIN ' named entity 'FUTURE' named entity 'NECESSARY' named entity 'MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS' named entity 'IFN' named entity 'EVALUATED' named entity 'INDUCED' named entity 'SWINE' named entity 'TARGETING' named entity 'STUDY' named entity 'EMERGENCE' named entity 'STUDIES' named entity 'TYPE I INTERFERON' named entity 'DESIGN' named entity 'VIRAL PATHOGENESIS' named entity 'PROPAGATION' named entity 'SIGNIFICANT' named entity 'OUTBREAK' named entity 'ACROSS' named entity 'ACTIVITY' named entity 'RELATIVE TO' named entity 'MUTANT' named entity 'UNDERSTANDING' named entity 'HAVE' named entity 'USE OF' named entity 'ENCODE' named entity 'PORCINE EPIDEMIC DIARRHEA VIRUS' named entity 'PARTIALLY' named entity 'EXAMINATION' named entity 'GLOBAL' named entity 'GENETIC ELEMENTS' named entity 'COVS' named entity 'CELL CULTURES' named entity 'IMPACT' named entity 'CHALLENGE' named entity 'THREAT' named entity 'AIRWAY'

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