About: Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2

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About: Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2 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	Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2
Creator	Ke, Changwen Rambaut, Andrew Zhang, Wei Wu, Jie Zhang, Huan Lu, Jing Yi, Lina Sun, Jiufeng Yuan, Runyu Li, Lin Liu, Zhe Zheng, Huanying Pybus, Oliver Bowden, Thomas Hulswit, Ruben Pfeiffer, Julie Li, Sun Li, Baisheng Li, Mingyue Lin, Huifang Loman, Nick Peng, Jinju Peng, Xiaofang Xiong, Qianling Liu, Citation Og, Pybus Peng, Yuan Rjg, Hulswit Ta, Bowden
source	Medline; PMC
abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus first identified in December 2019. Notable features that make SARS-CoV-2 distinct from most other previously identified betacoronaviruses include a receptor binding domain and a unique insertion of 12 nucleotides or 4 amino acids (PRRA) at the S1/S2 boundary. In this study, we identified two deletion variants of SARS-CoV-2 that either directly affect the polybasic cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN). These deletions were verified by multiple sequencing methods. In vitro results showed that the deletion of NSPRRAR likely does not affect virus replication in Vero and Vero-E6 cells; however, the deletion of QTQTN may restrict late-phase viral replication. The deletion of QTQTN was detected in 3 of 68 clinical samples and 12 of 24 in vitro-isolated viruses, while the deletion of NSPRRAR was identified in 3 in vitro-isolated viruses. Our data indicate that (i) there may be distinct selection pressures on SARS-CoV-2 replication or infection in vitro and in vivo; (ii) an efficient mechanism for deleting this region from the viral genome may exist, given that the deletion variant is commonly detected after two rounds of cell passage; and (iii) the PRRA insertion, which is unique to SARS-CoV-2, is not fixed during virus replication in vitro. These findings provide information to aid further investigation of SARS-CoV-2 infection mechanisms and a better understanding of the NSPRRAR deletion variant observed here. IMPORTANCE The spike protein determines the infectivity and host range of coronaviruses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has two unique features in its spike protein, the receptor binding domain and an insertion of 12 nucleotides at the S1/S2 boundary resulting in a furin-like cleavage site. Here, we identified two deletion variants of SARS-CoV-2 that either directly affect the furin-like cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN), and we investigated these deletions in cell isolates and clinical samples. The absence of the polybasic cleavage site in SARS-CoV-2 did not affect virus replication in Vero or Vero-E6 cells. Our data indicate the PRRAR sequence and the flanking QTQTN sequence are not fixed in vitro; thus, there appears to be distinct selection pressures on SARS-CoV-2 sequences in vitro and in vivo. Further investigation of the mechanism of generating these deletion variants and their infectivity in different animal models would improve our understanding of the origin and evolution of this virus.
has issue date	2020-08-17(xsd:dateTime)
bibo:doi	10.1128/jvi.00790-20
bibo:pmid	32571797
has license	no-cc
sha1sum (hex)	eda691f81ecdc39651e2ac0964f38813f700cf50
schema:url	https://doi.org/10.1128/jvi.00790-20
resource representing a document's title	Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2
has PubMed Central identifier	PMC7431800
has PubMed identifier	32571797
schema:publication	J Virol
resource representing a document's body	covid:eda691f81ecdc39651e2ac0964f38813f700cf50#body_text
is schema:about of	named entity 'deletion' named entity 'infection' named entity 'cell' named entity 'aid' named entity 'cells' named entity 'selection pressures' named entity 'commonly' named entity 'Severe Acute Respiratory Syndrome Coronavirus 2' named entity 'METHODS' named entity 'MAKE' named entity 'ROUNDS' named entity 'SELECTION' named entity 'OUR' named entity 'SARS-COV-2 REPLICATION' named entity 'VIRUS REPLICATION' named entity 'DOES NOT' named entity 'SARS-CoV-2' named entity 'replication' named entity 'deletions' named entity 'samples' named entity 'cleavage' named entity 'sequence' named entity 'Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)' named entity 'affect' named entity 'features' named entity 'SARS-CoV-2' named entity 'provide' named entity 'absence' named entity 'cells' named entity 'Identification' named entity 'nucleotides' named entity 'virus replication' named entity 'coronaviruses' named entity 'SARS-CoV-2' named entity 'betacoronaviruses' named entity 'Severe acute respiratory syndrome coronavirus 2' named entity 'viruses' named entity 'amino acids' named entity 'SARS-CoV-2' named entity 'SARS-CoV-2' named entity 'spike protein' named entity 'Deletions' named entity 'animal reservoir' named entity 'deletions' named entity 'inoculate' named entity 'SARS-COV-2' named entity 'high affinity' named entity 'Viral' named entity 'cleavage site' named entity 'SARS-CoV-2' named entity 'coronavirus 2' named entity 'SARS-CoV-2' named entity 'flow cell'

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