Genotypic and phenotypic resistance of pandemic A/H1N1 influenza viruses circulating in Germany.
Identifieur interne : 000294 ( Main/Exploration ); précédent : 000293; suivant : 000295Genotypic and phenotypic resistance of pandemic A/H1N1 influenza viruses circulating in Germany.
Auteurs : Susanne C. Duwe [Allemagne] ; Marianne Wedde ; Patricia Birkner ; Brunhilde SchweigerSource :
- Antiviral research [ 1872-9096 ] ; 2011.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Allemagne, Antiviraux (pharmacologie), Enfant, Enfant d'âge préscolaire, Femelle, Grippe humaine (virologie), Humains, Jeune adulte, Mutation faux-sens, Mâle, Oséltamivir (pharmacologie), Protéines de la matrice virale (génétique), Protéines virales (génétique), Résistance virale aux médicaments, Sialidase (génétique), Sous-type H1N1 du virus de la grippe A (), Sous-type H1N1 du virus de la grippe A (génétique), Sous-type H1N1 du virus de la grippe A (isolement et purification), Substitution d'acide aminé (génétique), Tests de sensibilité microbienne, Zanamivir (pharmacologie).
- MESH :
- génétique : Protéines de la matrice virale, Protéines virales, Sialidase, Sous-type H1N1 du virus de la grippe A, Substitution d'acide aminé.
- isolement et purification : Sous-type H1N1 du virus de la grippe A.
- pharmacologie : Antiviraux, Oséltamivir, Zanamivir.
- virologie : Grippe humaine.
- Adulte, Adulte d'âge moyen, Allemagne, Enfant, Enfant d'âge préscolaire, Femelle, Humains, Jeune adulte, Mutation faux-sens, Mâle, Résistance virale aux médicaments, Sous-type H1N1 du virus de la grippe A, Tests de sensibilité microbienne.
- Wicri :
- geographic : Allemagne.
English descriptors
- KwdEn :
- Adult, Amino Acid Substitution (genetics), Antiviral Agents (pharmacology), Child, Child, Preschool, Drug Resistance, Viral, Female, Germany, Humans, Influenza A Virus, H1N1 Subtype (drug effects), Influenza A Virus, H1N1 Subtype (genetics), Influenza A Virus, H1N1 Subtype (isolation & purification), Influenza, Human (virology), Male, Microbial Sensitivity Tests, Middle Aged, Mutation, Missense, Neuraminidase (genetics), Oseltamivir (pharmacology), Viral Matrix Proteins (genetics), Viral Proteins (genetics), Young Adult, Zanamivir (pharmacology).
- MESH :
- chemical , genetics : Neuraminidase, Viral Matrix Proteins, Viral Proteins.
- chemical , pharmacology : Antiviral Agents, Oseltamivir, Zanamivir.
- geographic : Germany.
- drug effects : Influenza A Virus, H1N1 Subtype.
- genetics : Amino Acid Substitution, Influenza A Virus, H1N1 Subtype.
- isolation & purification : Influenza A Virus, H1N1 Subtype.
- virology : Influenza, Human.
- Adult, Child, Child, Preschool, Drug Resistance, Viral, Female, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Mutation, Missense, Young Adult.
Abstract
In response to the rapid global spread of an antigenically novel A/H1N1 influenza virus in 2009, the World Heath Organization (WHO) recommended surveillance and monitoring for antiviral resistance of influenza viruses. We designed and evaluated pyrosequencing (PSQ)-based genotypic assays for high-throughput analysis of the susceptibility of pandemic A/H1N1 influenza viruses to neuraminidase (NA) inhibitors. A total of 1570 samples circulating in Germany between April 2009 and April 2010 were tested for determination of molecular markers of resistance to the NA inhibitors oseltamivir and zanamivir, and 635 of them were evaluated by phenotypic fluorescence-based assay with MUNANA substrate. Eight (0.5%) viruses were resistant to oseltamivir due to the H274Y NA substitution (N2 numbering). Six of these oseltamivir-resistant cases were treatment-related; four of them were selected in immunocompromised patients, two in patients suffered from chronic diseases. The two remaining oseltamivir-resistant viruses seem to have evolved in the absence of drug treatment and were isolated from immunocompetent healthy patients. All tested A/H1N1 pandemic viruses were sensitive to zanamivir. In addition, analysis of 1011 pandemic A/H1N1 virus samples by a PSQ-based assay according to the WHO protocol revealed the presence of mutation S31N in the M2 protein that conferred resistance to M2 ion channel inhibitors. Our data demonstrate a low incidence of oseltamivir-resistant pandemic A/H1N1 influenza variants isolated under drug selection pressure as well as community-acquired or naturally evolving viruses.
DOI: 10.1016/j.antiviral.2010.11.001
PubMed: 21070812
Affiliations:
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We designed and evaluated pyrosequencing (PSQ)-based genotypic assays for high-throughput analysis of the susceptibility of pandemic A/H1N1 influenza viruses to neuraminidase (NA) inhibitors. A total of 1570 samples circulating in Germany between April 2009 and April 2010 were tested for determination of molecular markers of resistance to the NA inhibitors oseltamivir and zanamivir, and 635 of them were evaluated by phenotypic fluorescence-based assay with MUNANA substrate. Eight (0.5%) viruses were resistant to oseltamivir due to the H274Y NA substitution (N2 numbering). Six of these oseltamivir-resistant cases were treatment-related; four of them were selected in immunocompromised patients, two in patients suffered from chronic diseases. The two remaining oseltamivir-resistant viruses seem to have evolved in the absence of drug treatment and were isolated from immunocompetent healthy patients. All tested A/H1N1 pandemic viruses were sensitive to zanamivir. In addition, analysis of 1011 pandemic A/H1N1 virus samples by a PSQ-based assay according to the WHO protocol revealed the presence of mutation S31N in the M2 protein that conferred resistance to M2 ion channel inhibitors. Our data demonstrate a low incidence of oseltamivir-resistant pandemic A/H1N1 influenza variants isolated under drug selection pressure as well as community-acquired or naturally evolving viruses.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21070812</PMID><DateCompleted><Year>2011</Year><Month>04</Month><Day>14</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1872-9096</ISSN><JournalIssue CitedMedium="Internet"><Volume>89</Volume><Issue>1</Issue><PubDate><Year>2011</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Antiviral research</Title><ISOAbbreviation>Antiviral Res.</ISOAbbreviation></Journal><ArticleTitle>Genotypic and phenotypic resistance of pandemic A/H1N1 influenza viruses circulating in Germany.</ArticleTitle><Pagination><MedlinePgn>115-8</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.antiviral.2010.11.001</ELocationID><Abstract><AbstractText>In response to the rapid global spread of an antigenically novel A/H1N1 influenza virus in 2009, the World Heath Organization (WHO) recommended surveillance and monitoring for antiviral resistance of influenza viruses. We designed and evaluated pyrosequencing (PSQ)-based genotypic assays for high-throughput analysis of the susceptibility of pandemic A/H1N1 influenza viruses to neuraminidase (NA) inhibitors. A total of 1570 samples circulating in Germany between April 2009 and April 2010 were tested for determination of molecular markers of resistance to the NA inhibitors oseltamivir and zanamivir, and 635 of them were evaluated by phenotypic fluorescence-based assay with MUNANA substrate. Eight (0.5%) viruses were resistant to oseltamivir due to the H274Y NA substitution (N2 numbering). Six of these oseltamivir-resistant cases were treatment-related; four of them were selected in immunocompromised patients, two in patients suffered from chronic diseases. The two remaining oseltamivir-resistant viruses seem to have evolved in the absence of drug treatment and were isolated from immunocompetent healthy patients. All tested A/H1N1 pandemic viruses were sensitive to zanamivir. In addition, analysis of 1011 pandemic A/H1N1 virus samples by a PSQ-based assay according to the WHO protocol revealed the presence of mutation S31N in the M2 protein that conferred resistance to M2 ion channel inhibitors. Our data demonstrate a low incidence of oseltamivir-resistant pandemic A/H1N1 influenza variants isolated under drug selection pressure as well as community-acquired or naturally evolving viruses.</AbstractText><CopyrightInformation>Copyright © 2010 Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Duwe</LastName><ForeName>Susanne C</ForeName><Initials>SC</Initials><AffiliationInfo><Affiliation>Robert Koch-Institut, National Reference Centre for Influenza, Nordufer 20, 13353 Berlin, Germany. 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MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005858" MajorTopicYN="N" Type="Geographic">Germany</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053118" MajorTopicYN="N">Influenza A Virus, H1N1 Subtype</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007251" MajorTopicYN="N">Influenza, Human</DescriptorName><QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008826" MajorTopicYN="N">Microbial Sensitivity Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020125" MajorTopicYN="N">Mutation, Missense</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009439" MajorTopicYN="N">Neuraminidase</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053139" MajorTopicYN="N">Oseltamivir</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014763" MajorTopicYN="N">Viral Matrix Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014764" MajorTopicYN="N">Viral Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053243" MajorTopicYN="N">Zanamivir</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2010</Year><Month>04</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2010</Year><Month>10</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2010</Year><Month>11</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>11</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>11</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2011</Year><Month>4</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">21070812</ArticleId><ArticleId IdType="pii">S0166-3542(10)00772-2</ArticleId><ArticleId IdType="doi">10.1016/j.antiviral.2010.11.001</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Allemagne</li></country><region><li>Berlin</li></region><settlement><li>Berlin</li></settlement></list><tree><noCountry><name sortKey="Birkner, Patricia" sort="Birkner, Patricia" uniqKey="Birkner P" first="Patricia" last="Birkner">Patricia Birkner</name><name sortKey="Schweiger, Brunhilde" sort="Schweiger, Brunhilde" uniqKey="Schweiger B" first="Brunhilde" last="Schweiger">Brunhilde Schweiger</name><name sortKey="Wedde, Marianne" sort="Wedde, Marianne" uniqKey="Wedde M" first="Marianne" last="Wedde">Marianne Wedde</name></noCountry><country name="Allemagne"><region name="Berlin"><name sortKey="Duwe, Susanne C" sort="Duwe, Susanne C" uniqKey="Duwe S" first="Susanne C" last="Duwe">Susanne C. 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