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Article: Intra-host non-synonymous diversity at a neutralizing antibody epitope of SARS-CoV-2 spike protein N-terminal domain

TitleIntra-host non-synonymous diversity at a neutralizing antibody epitope of SARS-CoV-2 spike protein N-terminal domain
Authors
KeywordsCOVID-19
Illumina sequencing
Intra-host diversity
Nanopore sequencing
Neutralizing antibody
Issue Date2021
PublisherElsevier Ltd. The Journal's web site is located at http://www.journals.elsevier.com/clinical-microbiology-and-infection/
Citation
Clinical Microbiology and Infection, 2021, v. 27 n. 9, p. 1350.e1-1350.e5 How to Cite?
AbstractObjectives: SARS-CoV-2 has evolved rapidly into several genetic clusters. However, data on mutations during the course of infection are scarce. This study aims to determine viral genome diversity in serial samples of COVID-19 patients. Methods: Targeted deep sequencing of the spike gene was performed on serial respiratory specimens from COVID-19 patients using nanopore and Illumina sequencing. Sanger sequencing was then performed to confirm the single nucleotide polymorphisms. Results: A total of 28 serial respiratory specimens from 12 patients were successfully sequenced using nanopore and Illumina sequencing. A 75-year-old patient with severe disease had a mutation, G22017T, identified in the second specimen. The frequency of G22017T increased from ≤5% (nanopore: 3.8%; Illumina: 5%) from the first respiratory tract specimen (sputum) to ≥60% (nanopore: 67.7%; Illumina: 60.4%) in the second specimen (saliva; collected 2 days after the first specimen). The difference in G22017T frequency was also confirmed by Sanger sequencing. G22017T corresponds to W152L amino acid mutation in the spike protein which was only found in <0.03% of the sequences deposited into a public database. Spike amino acid residue 152 is located within the N-terminal domain, which mediates the binding of a neutralizing antibody. Discussion: A spike protein amino acid mutation W152L located within a neutralizing epitope has appeared naturally in a patient. Our study demonstrated that monitoring of serial specimens is important in identifying hotspots of mutations, especially those occurring at neutralizing epitopes which may affect the therapeutic efficacy of monoclonal antibodies.
Persistent Identifierhttp://hdl.handle.net/10722/303976
ISSN
2020 Impact Factor: 8.067
2020 SCImago Journal Rankings: 2.884
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorIp, JD-
dc.contributor.authorKok, KH-
dc.contributor.authorChan, WM-
dc.contributor.authorChu, AWH-
dc.contributor.authorWu, wl-
dc.contributor.authorYip, CCY-
dc.contributor.authorTo, WK-
dc.contributor.authorTsang, OTY-
dc.contributor.authorLeung, WS-
dc.contributor.authorChik, TSH-
dc.contributor.authorChan, KH-
dc.contributor.authorHung, IFN-
dc.contributor.authorYuen, KY-
dc.contributor.authorTo, KKW-
dc.date.accessioned2021-09-23T08:53:28Z-
dc.date.available2021-09-23T08:53:28Z-
dc.date.issued2021-
dc.identifier.citationClinical Microbiology and Infection, 2021, v. 27 n. 9, p. 1350.e1-1350.e5-
dc.identifier.issn1198-743X-
dc.identifier.urihttp://hdl.handle.net/10722/303976-
dc.description.abstractObjectives: SARS-CoV-2 has evolved rapidly into several genetic clusters. However, data on mutations during the course of infection are scarce. This study aims to determine viral genome diversity in serial samples of COVID-19 patients. Methods: Targeted deep sequencing of the spike gene was performed on serial respiratory specimens from COVID-19 patients using nanopore and Illumina sequencing. Sanger sequencing was then performed to confirm the single nucleotide polymorphisms. Results: A total of 28 serial respiratory specimens from 12 patients were successfully sequenced using nanopore and Illumina sequencing. A 75-year-old patient with severe disease had a mutation, G22017T, identified in the second specimen. The frequency of G22017T increased from ≤5% (nanopore: 3.8%; Illumina: 5%) from the first respiratory tract specimen (sputum) to ≥60% (nanopore: 67.7%; Illumina: 60.4%) in the second specimen (saliva; collected 2 days after the first specimen). The difference in G22017T frequency was also confirmed by Sanger sequencing. G22017T corresponds to W152L amino acid mutation in the spike protein which was only found in <0.03% of the sequences deposited into a public database. Spike amino acid residue 152 is located within the N-terminal domain, which mediates the binding of a neutralizing antibody. Discussion: A spike protein amino acid mutation W152L located within a neutralizing epitope has appeared naturally in a patient. Our study demonstrated that monitoring of serial specimens is important in identifying hotspots of mutations, especially those occurring at neutralizing epitopes which may affect the therapeutic efficacy of monoclonal antibodies.-
dc.languageeng-
dc.publisherElsevier Ltd. The Journal's web site is located at http://www.journals.elsevier.com/clinical-microbiology-and-infection/-
dc.relation.ispartofClinical Microbiology and Infection-
dc.subjectCOVID-19-
dc.subjectIllumina sequencing-
dc.subjectIntra-host diversity-
dc.subjectNanopore sequencing-
dc.subjectNeutralizing antibody-
dc.titleIntra-host non-synonymous diversity at a neutralizing antibody epitope of SARS-CoV-2 spike protein N-terminal domain-
dc.typeArticle-
dc.identifier.emailKok, KH: khkok@hku.hk-
dc.identifier.emailChan, WM: mbally@hku.hk-
dc.identifier.emailChu, AWH: awhchu@hku.hk-
dc.identifier.emailWu, wl: alanklwu@hkucc.hku.hk-
dc.identifier.emailYip, CCY: yipcyril@hku.hk-
dc.identifier.emailChan, KH: chankh2@hkucc.hku.hk-
dc.identifier.emailHung, IFN: ivanhung@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailTo, KKW: kelvinto@hku.hk-
dc.identifier.authorityKok, KH=rp01455-
dc.identifier.authorityYip, CCY=rp01721-
dc.identifier.authorityChan, KH=rp01921-
dc.identifier.authorityHung, IFN=rp00508-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityTo, KKW=rp01384-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.cmi.2020.10.030-
dc.identifier.pmid33144203-
dc.identifier.pmcidPMC7605743-
dc.identifier.scopuseid_2-s2.0-85096855303-
dc.identifier.hkuros325583-
dc.identifier.volume27-
dc.identifier.issue9-
dc.identifier.spage1350.e1-
dc.identifier.epage1350.e5-
dc.identifier.isiWOS:000691800900031-
dc.publisher.placeUnited Kingdom-

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