About: Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization

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About: Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization 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
has title	Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization
Creator	Drosten, Christian Pöhlmann, Stefan Hoffmann, Markus Kleine-Weber, Hannah Wang, Lingshu Müller, Marcel Graham, Barney Elzayat, Mahmoud
topic	covid:f0f1ec9f037c5141e44411f686d908fe3a15d223#this
Source	Medline; PMC
abstract	Middle East respiratory syndrome coronavirus (MERS-CoV) poses a threat to public health. The virus is endemic in the Middle East but can be transmitted to other countries by travel activity. The introduction of MERS-CoV into the Republic of Korea by an infected traveler resulted in a hospital outbreak of MERS that entailed 186 cases and 38 deaths. The MERS-CoV spike (S) protein binds to the cellular protein DPP4 via its receptor binding domain (RBD) and mediates viral entry into target cells. During the MERS outbreak in Korea, emergence and spread of viral variants that harbored mutations in the RBD, D510G and I529T, was observed. Counterintuitively, these mutations were found to reduce DPP4 binding and viral entry into target cells. In this study, we investigated whether they also exerted proviral effects. We confirm that changes D510G and I529T reduce S protein binding to DPP4 but show that this reduction only translates into diminished viral entry when expression of DPP4 on target cells is low. Neither mutation modulated S protein binding to sialic acids, S protein activation by host cell proteases, or inhibition of S protein-driven entry by interferon-induced transmembrane proteins. In contrast, changes D510G and I529T increased resistance of S protein-driven entry to neutralization by monoclonal antibodies and sera from MERS patients. These findings indicate that MERS-CoV variants with reduced neutralization sensitivity were transmitted during the Korean outbreak and that the responsible mutations were compatible with robust infection of cells expressing high levels of DPP4. IMPORTANCE MERS-CoV has pandemic potential, and it is important to identify mutations in viral proteins that might augment viral spread. In the course of a large hospital outbreak of MERS in the Republic of Korea in 2015, the spread of a viral variant that contained mutations in the viral spike protein was observed. These mutations were found to reduce receptor binding and viral infectivity. However, it remained unclear whether they also exerted proviral effects. We demonstrate that these mutations reduce sensitivity to antibody-mediated neutralization and are compatible with robust infection of target cells expressing large amounts of the viral receptor DPP4.
has issue date	2018-11-07(xsd:dateTime)
bibo:doi	10.1128/jvi.01381-18
bibo:pmid	30404801
has license	bronze-oa
sha1sum (hex)	f0f1ec9f037c5141e44411f686d908fe3a15d223
schema:url	https://doi.org/10.1128/jvi.01381-18
resource representing a document's title	Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization
has PubMed Central identifier	PMC6321919
has PubMed identifier	30404801
schema:publication	Journal of Virology
resource representing a document's body	covid:f0f1ec9f037c5141e44411f686d908fe3a15d223#body_text
is http://vocab.deri.ie/void#inDataset of	https://covidontheweb.inria.fr:4443/about/id/http/ns.inria.fr/covid19/f0f1ec9f037c5141e44411f686d908fe3a15d223
is schema:about of	named entity 'DPP4' named entity 'mediates' named entity 'neutralization' named entity 'hospital' named entity 'DPP4' named entity 'transmembrane proteins' named entity 'protein' named entity 'observed' named entity 'confirm' named entity 'travel' named entity 'reduce' named entity 'levels' named entity 'The' named entity 'mutations' named entity 'MERS outbreak' named entity 'Resistance' named entity 'TRANSMEMBRANE PROTEINS' named entity 'SPREAD' named entity 'CHANGES' named entity 'OUTBREAK' named entity 'REDUCED' named entity 'UNCLEAR' named entity 'KOREA' named entity 'TO IDENTIFY' named entity 'ANTIBODY-MEDIATED NEUTRALIZATION' named entity 'AUGMENT' named entity 'AMOUNTS' named entity 'EFFECTS' named entity '28S' named entity 'INVESTIGATED' named entity 'EXERTED' named entity 'LEVELS' named entity 'VARIANTS' named entity 'LARGE' named entity 'DIMINISHED' named entity '2015' named entity 'VIRAL' named entity 'ENDEMIC' named entity 'SIALIC ACIDS' named entity 'CONFIRM' named entity 'BINDING' named entity 'viral' named entity 'infection' named entity 'binding' named entity 'Korean' named entity 'viral entry' named entity 'public health' named entity 'target cells' named entity 'Neither' named entity 'infected' named entity 'binds' named entity 'viral' named entity 'reduce' named entity 'neutralization' named entity 'Korea' named entity 'MERS-CoV' named entity 'RBD' named entity 'transmitted' named entity '2015' named entity 'mutations' named entity 'hospital' named entity 'infection' named entity 'Korean outbreak' named entity 'receptor binding' named entity 'protein binding' named entity 'viral entry' named entity 'MERS' named entity 'protein binding' named entity 'interferon' named entity 'Middle East respiratory syndrome coronavirus' named entity 'proviral' named entity 'Republic of Korea'

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