The Molecular Basis for Antigenic Drift of Human A/H2N2 Influenza Viruses.
Identifieur interne : 000009 ( PubMed/Corpus ); précédent : 000008; suivant : 000010The Molecular Basis for Antigenic Drift of Human A/H2N2 Influenza Viruses.
Auteurs : M. Linster ; E J A. Schrauwen ; S. Van Der Vliet ; D F Burke ; P. Lexmond ; T M Bestebroer ; D J Smith ; S. Herfst ; B F Koel ; R A M. FouchierSource :
- Journal of virology [ 1098-5514 ] ; 2019.
English descriptors
- KwdEn :
- Amino Acid Substitution, Animals, Antigens, Viral (genetics), Antigens, Viral (immunology), Dogs, Evolution, Molecular, Ferrets, Hemagglutinin Glycoproteins, Influenza Virus (genetics), Hemagglutinin Glycoproteins, Influenza Virus (immunology), Humans, Influenza A Virus, H2N2 Subtype (genetics), Influenza A Virus, H2N2 Subtype (immunology), Influenza, Human (epidemiology), Influenza, Human (genetics), Influenza, Human (immunology), Madin Darby Canine Kidney Cells, Mutation, Missense, Pandemics, Time Factors.
- MESH :
- chemical , genetics : Antigens, Viral, Hemagglutinin Glycoproteins, Influenza Virus.
- chemical , immunology : Antigens, Viral, Hemagglutinin Glycoproteins, Influenza Virus.
- epidemiology : Influenza, Human.
- genetics : Influenza A Virus, H2N2 Subtype, Influenza, Human.
- immunology : Influenza A Virus, H2N2 Subtype, Influenza, Human.
- Amino Acid Substitution, Animals, Dogs, Evolution, Molecular, Ferrets, Humans, Madin Darby Canine Kidney Cells, Mutation, Missense, Pandemics, Time Factors.
Abstract
Influenza A/H2N2 viruses caused a pandemic in 1957 and continued to circulate in humans until 1968. The antigenic evolution of A/H2N2 viruses over time and the amino acid substitutions responsible for this antigenic evolution are not known. Here, the antigenic diversity of a representative set of human A/H2N2 viruses isolated between 1957 and 1968 was characterized. The antigenic change of influenza A/H2N2 viruses during the 12 years that this virus circulated was modest. Two amino acid substitutions, T128D and N139K, located in the head domain of the H2 hemagglutinin (HA) molecule, were identified as important determinants of antigenic change during A/H2N2 virus evolution. The rate of A/H2N2 virus antigenic evolution during the 12-year period after introduction in humans was half that of A/H3N2 viruses, despite similar rates of genetic change.IMPORTANCE While influenza A viruses of subtype H2N2 were at the origin of the Asian influenza pandemic, little is known about the antigenic changes that occurred during the twelve years of circulation in humans, the role of preexisting immunity, and the evolutionary rates of the virus. In this study, the antigenic map derived from hemagglutination inhibition (HI) titers of cell-cultured virus isolates and ferret postinfection sera displayed a directional evolution of viruses away from earlier isolates. Furthermore, individual mutations in close proximity to the receptor-binding site of the HA molecule determined the antigenic reactivity, confirming that individual amino acid substitutions in A/H2N2 viruses can confer major antigenic changes. This study adds to our understanding of virus evolution with respect to antigenic variability, rates of virus evolution, and potential escape mutants of A/H2N2.
DOI: 10.1128/JVI.01907-18
PubMed: 30700609
Links to Exploration step
pubmed:30700609Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The Molecular Basis for Antigenic Drift of Human A/H2N2 Influenza Viruses.</title><author><name sortKey="Linster, M" sort="Linster, M" uniqKey="Linster M" first="M" last="Linster">M. Linster</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Schrauwen, E J A" sort="Schrauwen, E J A" uniqKey="Schrauwen E" first="E J A" last="Schrauwen">E J A. Schrauwen</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Der Vliet, S" sort="Van Der Vliet, S" uniqKey="Van Der Vliet S" first="S" last="Van Der Vliet">S. Van Der Vliet</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Burke, D F" sort="Burke, D F" uniqKey="Burke D" first="D F" last="Burke">D F Burke</name><affiliation><nlm:affiliation>Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Lexmond, P" sort="Lexmond, P" uniqKey="Lexmond P" first="P" last="Lexmond">P. Lexmond</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Bestebroer, T M" sort="Bestebroer, T M" uniqKey="Bestebroer T" first="T M" last="Bestebroer">T M Bestebroer</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Smith, D J" sort="Smith, D J" uniqKey="Smith D" first="D J" last="Smith">D J Smith</name><affiliation><nlm:affiliation>Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Herfst, S" sort="Herfst, S" uniqKey="Herfst S" first="S" last="Herfst">S. Herfst</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Koel, B F" sort="Koel, B F" uniqKey="Koel B" first="B F" last="Koel">B F Koel</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Fouchier, R A M" sort="Fouchier, R A M" uniqKey="Fouchier R" first="R A M" last="Fouchier">R A M. Fouchier</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands r.fouchier@erasmusmc.nl.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:30700609</idno><idno type="pmid">30700609</idno><idno type="doi">10.1128/JVI.01907-18</idno><idno type="wicri:Area/PubMed/Corpus">000009</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000009</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The Molecular Basis for Antigenic Drift of Human A/H2N2 Influenza Viruses.</title><author><name sortKey="Linster, M" sort="Linster, M" uniqKey="Linster M" first="M" last="Linster">M. Linster</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Schrauwen, E J A" sort="Schrauwen, E J A" uniqKey="Schrauwen E" first="E J A" last="Schrauwen">E J A. Schrauwen</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Der Vliet, S" sort="Van Der Vliet, S" uniqKey="Van Der Vliet S" first="S" last="Van Der Vliet">S. Van Der Vliet</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Burke, D F" sort="Burke, D F" uniqKey="Burke D" first="D F" last="Burke">D F Burke</name><affiliation><nlm:affiliation>Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Lexmond, P" sort="Lexmond, P" uniqKey="Lexmond P" first="P" last="Lexmond">P. Lexmond</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Bestebroer, T M" sort="Bestebroer, T M" uniqKey="Bestebroer T" first="T M" last="Bestebroer">T M Bestebroer</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Smith, D J" sort="Smith, D J" uniqKey="Smith D" first="D J" last="Smith">D J Smith</name><affiliation><nlm:affiliation>Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Herfst, S" sort="Herfst, S" uniqKey="Herfst S" first="S" last="Herfst">S. Herfst</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Koel, B F" sort="Koel, B F" uniqKey="Koel B" first="B F" last="Koel">B F Koel</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Fouchier, R A M" sort="Fouchier, R A M" uniqKey="Fouchier R" first="R A M" last="Fouchier">R A M. Fouchier</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands r.fouchier@erasmusmc.nl.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Substitution</term><term>Animals</term><term>Antigens, Viral (genetics)</term><term>Antigens, Viral (immunology)</term><term>Dogs</term><term>Evolution, Molecular</term><term>Ferrets</term><term>Hemagglutinin Glycoproteins, Influenza Virus (genetics)</term><term>Hemagglutinin Glycoproteins, Influenza Virus (immunology)</term><term>Humans</term><term>Influenza A Virus, H2N2 Subtype (genetics)</term><term>Influenza A Virus, H2N2 Subtype (immunology)</term><term>Influenza, Human (epidemiology)</term><term>Influenza, Human (genetics)</term><term>Influenza, Human (immunology)</term><term>Madin Darby Canine Kidney Cells</term><term>Mutation, Missense</term><term>Pandemics</term><term>Time Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antigens, Viral</term><term>Hemagglutinin Glycoproteins, Influenza Virus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Viral</term><term>Hemagglutinin Glycoproteins, Influenza Virus</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza A Virus, H2N2 Subtype</term><term>Influenza, Human</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Influenza A Virus, H2N2 Subtype</term><term>Influenza, Human</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Substitution</term><term>Animals</term><term>Dogs</term><term>Evolution, Molecular</term><term>Ferrets</term><term>Humans</term><term>Madin Darby Canine Kidney Cells</term><term>Mutation, Missense</term><term>Pandemics</term><term>Time Factors</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Influenza A/H2N2 viruses caused a pandemic in 1957 and continued to circulate in humans until 1968. The antigenic evolution of A/H2N2 viruses over time and the amino acid substitutions responsible for this antigenic evolution are not known. Here, the antigenic diversity of a representative set of human A/H2N2 viruses isolated between 1957 and 1968 was characterized. The antigenic change of influenza A/H2N2 viruses during the 12 years that this virus circulated was modest. Two amino acid substitutions, T128D and N139K, located in the head domain of the H2 hemagglutinin (HA) molecule, were identified as important determinants of antigenic change during A/H2N2 virus evolution. The rate of A/H2N2 virus antigenic evolution during the 12-year period after introduction in humans was half that of A/H3N2 viruses, despite similar rates of genetic change.<b>IMPORTANCE</b> While influenza A viruses of subtype H2N2 were at the origin of the Asian influenza pandemic, little is known about the antigenic changes that occurred during the twelve years of circulation in humans, the role of preexisting immunity, and the evolutionary rates of the virus. In this study, the antigenic map derived from hemagglutination inhibition (HI) titers of cell-cultured virus isolates and ferret postinfection sera displayed a directional evolution of viruses away from earlier isolates. Furthermore, individual mutations in close proximity to the receptor-binding site of the HA molecule determined the antigenic reactivity, confirming that individual amino acid substitutions in A/H2N2 viruses can confer major antigenic changes. This study adds to our understanding of virus evolution with respect to antigenic variability, rates of virus evolution, and potential escape mutants of A/H2N2.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30700609</PMID><DateCompleted><Year>2020</Year><Month>01</Month><Day>28</Day></DateCompleted><DateRevised><Year>2020</Year><Month>03</Month><Day>09</Day></DateRevised><Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">1098-5514</ISSN><JournalIssue CitedMedium="Internet"><Volume>93</Volume><Issue>8</Issue><PubDate><Year>2019</Year><Month>04</Month><Day>15</Day></PubDate></JournalIssue><Title>Journal of virology</Title><ISOAbbreviation>J. Virol.</ISOAbbreviation></Journal><ArticleTitle>The Molecular Basis for Antigenic Drift of Human A/H2N2 Influenza Viruses.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">e01907-18</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1128/JVI.01907-18</ELocationID><Abstract><AbstractText>Influenza A/H2N2 viruses caused a pandemic in 1957 and continued to circulate in humans until 1968. The antigenic evolution of A/H2N2 viruses over time and the amino acid substitutions responsible for this antigenic evolution are not known. Here, the antigenic diversity of a representative set of human A/H2N2 viruses isolated between 1957 and 1968 was characterized. The antigenic change of influenza A/H2N2 viruses during the 12 years that this virus circulated was modest. Two amino acid substitutions, T128D and N139K, located in the head domain of the H2 hemagglutinin (HA) molecule, were identified as important determinants of antigenic change during A/H2N2 virus evolution. The rate of A/H2N2 virus antigenic evolution during the 12-year period after introduction in humans was half that of A/H3N2 viruses, despite similar rates of genetic change.<b>IMPORTANCE</b> While influenza A viruses of subtype H2N2 were at the origin of the Asian influenza pandemic, little is known about the antigenic changes that occurred during the twelve years of circulation in humans, the role of preexisting immunity, and the evolutionary rates of the virus. In this study, the antigenic map derived from hemagglutination inhibition (HI) titers of cell-cultured virus isolates and ferret postinfection sera displayed a directional evolution of viruses away from earlier isolates. Furthermore, individual mutations in close proximity to the receptor-binding site of the HA molecule determined the antigenic reactivity, confirming that individual amino acid substitutions in A/H2N2 viruses can confer major antigenic changes. This study adds to our understanding of virus evolution with respect to antigenic variability, rates of virus evolution, and potential escape mutants of A/H2N2.</AbstractText><CopyrightInformation>Copyright © 2019 American Society for Microbiology.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Linster</LastName><ForeName>M</ForeName><Initials>M</Initials><Identifier Source="ORCID">0000-0003-2636-2512</Identifier><AffiliationInfo><Affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Schrauwen</LastName><ForeName>E J A</ForeName><Initials>EJA</Initials><AffiliationInfo><Affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Avans University of Applied Science, Breda, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van der Vliet</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Burke</LastName><ForeName>D F</ForeName><Initials>DF</Initials><AffiliationInfo><Affiliation>Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lexmond</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bestebroer</LastName><ForeName>T M</ForeName><Initials>TM</Initials><AffiliationInfo><Affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smith</LastName><ForeName>D J</ForeName><Initials>DJ</Initials><AffiliationInfo><Affiliation>Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Herfst</LastName><ForeName>S</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0001-9866-8903</Identifier><AffiliationInfo><Affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Koel</LastName><ForeName>B F</ForeName><Initials>BF</Initials><Identifier Source="ORCID">0000-0003-4692-3989</Identifier><AffiliationInfo><Affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medical Microbiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fouchier</LastName><ForeName>R A M</ForeName><Initials>RAM</Initials><AffiliationInfo><Affiliation>Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands r.fouchier@erasmusmc.nl.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>DP1 OD000490</GrantID><Acronym>OD</Acronym><Agency>NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>HHSN272201400008C</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>04</Month><Day>03</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Virol</MedlineTA><NlmUniqueID>0113724</NlmUniqueID><ISSNLinking>0022-538X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000956">Antigens, Viral</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019267">Hemagglutinin Glycoproteins, Influenza Virus</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C483468">hemagglutinin, human influenza A virus</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D019943" MajorTopicYN="Y">Amino Acid Substitution</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000956" MajorTopicYN="Y">Antigens, Viral</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004285" MajorTopicYN="N">Dogs</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019143" MajorTopicYN="Y">Evolution, Molecular</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005289" MajorTopicYN="N">Ferrets</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019267" MajorTopicYN="Y">Hemagglutinin Glycoproteins, Influenza Virus</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053121" MajorTopicYN="Y">Influenza A Virus, H2N2 Subtype</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007251" MajorTopicYN="Y">Influenza, Human</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D061985" MajorTopicYN="N">Madin Darby Canine Kidney Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020125" MajorTopicYN="N">Mutation, Missense</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058873" MajorTopicYN="Y">Pandemics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time 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