Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape.
Identifieur interne : 000082 ( PubMed/Curation ); précédent : 000081; suivant : 000083Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape.
Auteurs : Friederike Feldmann [Canada] ; Darwyn Kobasa [Canada] ; Carissa Embury-Hyatt [Canada] ; Allen Grolla [Canada] ; Tracy Taylor [Canada] ; Maki Kiso [Japon] ; Satoshi Kakugawa [Japon] ; Jason Gren [Canada] ; Steven M. Jones [Canada] ; Yoshihiro Kawaoka [États-Unis] ; Heinz Feldmann [États-Unis]Source :
- mBio [ 2150-7511 ] ; 2019.
Descripteurs français
- KwdFr :
- MESH :
- pathogénicité : Sous-type H1N1 du virus de la grippe A.
- traitement médicamenteux : Infections à Orthomyxoviridae.
- usage thérapeutique : Oséltamivir.
- virologie : Infections à Orthomyxoviridae.
- Animaux, Macaca, Sous-type H1N1 du virus de la grippe A.
English descriptors
- KwdEn :
- MESH :
- chemical , therapeutic use : Oseltamivir.
- drug effects : Influenza A Virus, H1N1 Subtype.
- drug therapy : Orthomyxoviridae Infections.
- pathogenicity : Influenza A Virus, H1N1 Subtype.
- virology : Orthomyxoviridae Infections.
- Animals, Macaca.
Abstract
The 1918 influenza virus, subtype H1N1, was the causative agent of the most devastating pandemic in the history of infectious diseases. In vitro studies have confirmed that extreme virulence is an inherent property of this virus. Here, we utilized the macaque model for evaluating the efficacy of oseltamivir phosphate against the fully reconstructed 1918 influenza virus in a highly susceptible and relevant disease model. Our findings demonstrate that oseltamivir phosphate is effective in preventing severe disease in macaques but vulnerable to virus escape through emergence of resistant mutants, especially if given in a treatment regimen. Nevertheless, we conclude that oseltamivir would be highly beneficial to reduce the morbidity and mortality rates caused by a highly pathogenic influenza virus although it would be predicted that resistance would likely emerge with sustained use of the drug.IMPORTANCE Oseltamivir phosphate is used as a first line of defense in the event of an influenza pandemic prior to vaccine administration. Treatment failure through selection and replication of drug-resistant viruses is a known complication in the field and was also demonstrated in our study with spread of resistant 1918 influenza virus in multiple respiratory tissues. This emphasizes the importance of early treatment and the possibility that noncompliance may exacerbate treatment effectiveness. It also demonstrates the importance of implementing combination therapy and vaccination strategies as soon as possible in a pandemic situation.
DOI: 10.1128/mBio.02059-19
PubMed: 31641086
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Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea></affiliation></author><author><name sortKey="Embury Hyatt, Carissa" sort="Embury Hyatt, Carissa" uniqKey="Embury Hyatt C" first="Carissa" last="Embury-Hyatt">Carissa Embury-Hyatt</name><affiliation wicri:level="1"><nlm:affiliation>National Centre for Foreign Animal Diseases, Canadian Food Inspection Agency, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>National Centre for Foreign Animal Diseases, Canadian Food Inspection Agency, Winnipeg, Manitoba</wicri:regionArea></affiliation></author><author><name sortKey="Grolla, Allen" sort="Grolla, Allen" uniqKey="Grolla A" first="Allen" last="Grolla">Allen Grolla</name><affiliation wicri:level="1"><nlm:affiliation>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea></affiliation></author><author><name sortKey="Taylor, Tracy" sort="Taylor, Tracy" uniqKey="Taylor T" first="Tracy" last="Taylor">Tracy Taylor</name><affiliation wicri:level="1"><nlm:affiliation>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea></affiliation></author><author><name sortKey="Kiso, Maki" sort="Kiso, Maki" uniqKey="Kiso M" first="Maki" last="Kiso">Maki Kiso</name><affiliation wicri:level="1"><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Kakugawa, Satoshi" sort="Kakugawa, Satoshi" uniqKey="Kakugawa S" first="Satoshi" last="Kakugawa">Satoshi Kakugawa</name><affiliation wicri:level="1"><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Gren, Jason" sort="Gren, Jason" uniqKey="Gren J" first="Jason" last="Gren">Jason Gren</name><affiliation wicri:level="1"><nlm:affiliation>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea></affiliation></author><author><name sortKey="Jones, Steven M" sort="Jones, Steven M" uniqKey="Jones S" first="Steven M" last="Jones">Steven M. Jones</name><affiliation wicri:level="1"><nlm:affiliation>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea></affiliation></author><author><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><affiliation wicri:level="1"><nlm:affiliation>Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan kawaokay@svm.vetmed.wisc.edu feldmannh@niaid.nih.gov.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><affiliation wicri:level="1"><nlm:affiliation>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada kawaokay@svm.vetmed.wisc.edu feldmannh@niaid.nih.gov.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea></affiliation></author></analytic><series><title level="j">mBio</title><idno type="eISSN">2150-7511</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Influenza A Virus, H1N1 Subtype (drug effects)</term><term>Influenza A Virus, H1N1 Subtype (pathogenicity)</term><term>Macaca</term><term>Orthomyxoviridae Infections (drug therapy)</term><term>Orthomyxoviridae Infections (virology)</term><term>Oseltamivir (therapeutic use)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Infections à Orthomyxoviridae (traitement médicamenteux)</term><term>Infections à Orthomyxoviridae (virologie)</term><term>Macaca</term><term>Oséltamivir (usage thérapeutique)</term><term>Sous-type H1N1 du virus de la grippe A ()</term><term>Sous-type H1N1 du virus de la grippe A (pathogénicité)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Oseltamivir</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Sous-type H1N1 du virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à Orthomyxoviridae</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Oséltamivir</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à Orthomyxoviridae</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Macaca</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Macaca</term><term>Sous-type H1N1 du virus de la grippe A</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The 1918 influenza virus, subtype H1N1, was the causative agent of the most devastating pandemic in the history of infectious diseases. <i>In vitro</i> studies have confirmed that extreme virulence is an inherent property of this virus. Here, we utilized the macaque model for evaluating the efficacy of oseltamivir phosphate against the fully reconstructed 1918 influenza virus in a highly susceptible and relevant disease model. Our findings demonstrate that oseltamivir phosphate is effective in preventing severe disease in macaques but vulnerable to virus escape through emergence of resistant mutants, especially if given in a treatment regimen. Nevertheless, we conclude that oseltamivir would be highly beneficial to reduce the morbidity and mortality rates caused by a highly pathogenic influenza virus although it would be predicted that resistance would likely emerge with sustained use of the drug.<b>IMPORTANCE</b> Oseltamivir phosphate is used as a first line of defense in the event of an influenza pandemic prior to vaccine administration. Treatment failure through selection and replication of drug-resistant viruses is a known complication in the field and was also demonstrated in our study with spread of resistant 1918 influenza virus in multiple respiratory tissues. This emphasizes the importance of early treatment and the possibility that noncompliance may exacerbate treatment effectiveness. It also demonstrates the importance of implementing combination therapy and vaccination strategies as soon as possible in a pandemic situation.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31641086</PMID><DateCompleted><Year>2020</Year><Month>05</Month><Day>18</Day></DateCompleted><DateRevised><Year>2020</Year><Month>05</Month><Day>18</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2150-7511</ISSN><JournalIssue CitedMedium="Internet"><Volume>10</Volume><Issue>5</Issue><PubDate><Year>2019</Year><Month>10</Month><Day>22</Day></PubDate></JournalIssue><Title>mBio</Title><ISOAbbreviation>mBio</ISOAbbreviation></Journal><ArticleTitle>Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">e02059-19</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1128/mBio.02059-19</ELocationID><Abstract><AbstractText>The 1918 influenza virus, subtype H1N1, was the causative agent of the most devastating pandemic in the history of infectious diseases. <i>In vitro</i> studies have confirmed that extreme virulence is an inherent property of this virus. Here, we utilized the macaque model for evaluating the efficacy of oseltamivir phosphate against the fully reconstructed 1918 influenza virus in a highly susceptible and relevant disease model. Our findings demonstrate that oseltamivir phosphate is effective in preventing severe disease in macaques but vulnerable to virus escape through emergence of resistant mutants, especially if given in a treatment regimen. Nevertheless, we conclude that oseltamivir would be highly beneficial to reduce the morbidity and mortality rates caused by a highly pathogenic influenza virus although it would be predicted that resistance would likely emerge with sustained use of the drug.<b>IMPORTANCE</b> Oseltamivir phosphate is used as a first line of defense in the event of an influenza pandemic prior to vaccine administration. Treatment failure through selection and replication of drug-resistant viruses is a known complication in the field and was also demonstrated in our study with spread of resistant 1918 influenza virus in multiple respiratory tissues. This emphasizes the importance of early treatment and the possibility that noncompliance may exacerbate treatment effectiveness. It also demonstrates the importance of implementing combination therapy and vaccination strategies as soon as possible in a pandemic situation.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Feldmann</LastName><ForeName>Friederike</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Kobasa</LastName><ForeName>Darwyn</ForeName><Initials>D</Initials><Identifier Source="ORCID">0000-0002-6371-7493</Identifier><AffiliationInfo><Affiliation>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Embury-Hyatt</LastName><ForeName>Carissa</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>National Centre for Foreign Animal Diseases, Canadian Food Inspection Agency, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Grolla</LastName><ForeName>Allen</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Taylor</LastName><ForeName>Tracy</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kiso</LastName><ForeName>Maki</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kakugawa</LastName><ForeName>Satoshi</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gren</LastName><ForeName>Jason</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jones</LastName><ForeName>Steven M</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kawaoka</LastName><ForeName>Yoshihiro</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan kawaokay@svm.vetmed.wisc.edu feldmannh@niaid.nih.gov.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Feldmann</LastName><ForeName>Heinz</ForeName><Initials>H</Initials><Identifier Source="ORCID">0000-0001-9448-8227</Identifier><AffiliationInfo><Affiliation>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada kawaokay@svm.vetmed.wisc.edu feldmannh@niaid.nih.gov.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052060">Research Support, N.I.H., Intramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>10</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>mBio</MedlineTA><NlmUniqueID>101519231</NlmUniqueID></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>20O93L6F9H</RegistryNumber><NameOfSubstance UI="D053139">Oseltamivir</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053118" MajorTopicYN="N">Influenza A Virus, H1N1 Subtype</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000472" MajorTopicYN="Y">pathogenicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008251" MajorTopicYN="N">Macaca</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009976" MajorTopicYN="N">Orthomyxoviridae Infections</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053139" MajorTopicYN="N">Oseltamivir</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">1918 influenza virus</Keyword><Keyword MajorTopicYN="Y">drug resistance</Keyword><Keyword MajorTopicYN="Y">oseltamivir</Keyword><Keyword MajorTopicYN="Y">treatment</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>10</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>10</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>5</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31641086</ArticleId><ArticleId IdType="pii">mBio.02059-19</ArticleId><ArticleId IdType="doi">10.1128/mBio.02059-19</ArticleId><ArticleId IdType="pmc">PMC6805992</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Science. 2007 Feb 2;315(5812):655-9</Citation><ArticleIdList><ArticleId IdType="pubmed">17272724</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2013 May 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