A Single Amino Acid Substitution at Residue 218 of Hemagglutinin Improves the Growth of Influenza A(H7N9) Candidate Vaccine Viruses
Identifieur interne : 001F74 ( Ncbi/Merge ); précédent : 001F73; suivant : 001F75A Single Amino Acid Substitution at Residue 218 of Hemagglutinin Improves the Growth of Influenza A(H7N9) Candidate Vaccine Viruses
Auteurs : Xing Li [États-Unis] ; Yamei Gao [États-Unis] ; Zhiping Ye [États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 2019.
Descripteurs français
- KwdFr :
- Adaptation biologique, Analyse de survie, Animaux, Attachement viral, Cellules rénales canines Madin-Darby, Chiens, Embryon de poulet, Furets, Glycoprotéine hémagglutinine du virus influenza (génétique), Glycoprotéine hémagglutinine du virus influenza (métabolisme), Infections à Orthomyxoviridae (), Modèles animaux de maladie humaine, Protéines mutantes (génétique), Protéines mutantes (métabolisme), Réplication virale, Sous-type H7N9 du virus de la grippe A (croissance et développement), Sous-type H7N9 du virus de la grippe A (génétique), Sous-type H7N9 du virus de la grippe A (immunologie), Substitution d'acide aminé, Vaccins antigrippaux (administration et posologie), Vaccins antigrippaux (génétique), Vaccins antigrippaux (immunologie), Vaccins atténués (administration et posologie), Vaccins atténués (génétique), Vaccins atténués (immunologie), Virus recombinants (croissance et développement), Virus recombinants (génétique).
- MESH :
- administration et posologie : Vaccins antigrippaux, Vaccins atténués.
- croissance et développement : Sous-type H7N9 du virus de la grippe A, Virus recombinants.
- génétique : Glycoprotéine hémagglutinine du virus influenza, Protéines mutantes, Sous-type H7N9 du virus de la grippe A, Vaccins antigrippaux, Vaccins atténués, Virus recombinants.
- immunologie : Sous-type H7N9 du virus de la grippe A, Vaccins antigrippaux, Vaccins atténués.
- métabolisme : Glycoprotéine hémagglutinine du virus influenza, Protéines mutantes.
- Adaptation biologique, Analyse de survie, Animaux, Attachement viral, Cellules rénales canines Madin-Darby, Chiens, Embryon de poulet, Furets, Infections à Orthomyxoviridae, Modèles animaux de maladie humaine, Réplication virale, Substitution d'acide aminé.
English descriptors
- KwdEn :
- Adaptation, Biological, Amino Acid Substitution, Animals, Chick Embryo, Disease Models, Animal, Dogs, Ferrets, Hemagglutinin Glycoproteins, Influenza Virus (genetics), Hemagglutinin Glycoproteins, Influenza Virus (metabolism), Influenza A Virus, H7N9 Subtype (genetics), Influenza A Virus, H7N9 Subtype (growth & development), Influenza A Virus, H7N9 Subtype (immunology), Influenza Vaccines (administration & dosage), Influenza Vaccines (genetics), Influenza Vaccines (immunology), Madin Darby Canine Kidney Cells, Mutant Proteins (genetics), Mutant Proteins (metabolism), Orthomyxoviridae Infections (prevention & control), Reassortant Viruses (genetics), Reassortant Viruses (growth & development), Survival Analysis, Vaccines, Attenuated (administration & dosage), Vaccines, Attenuated (genetics), Vaccines, Attenuated (immunology), Virus Attachment, Virus Replication.
- MESH :
- chemical , administration & dosage : Influenza Vaccines, Vaccines, Attenuated.
- chemical , genetics : Hemagglutinin Glycoproteins, Influenza Virus, Influenza Vaccines, Mutant Proteins, Vaccines, Attenuated.
- chemical , immunology : Influenza Vaccines, Vaccines, Attenuated.
- chemical , metabolism : Hemagglutinin Glycoproteins, Influenza Virus, Mutant Proteins.
- genetics : Influenza A Virus, H7N9 Subtype, Reassortant Viruses.
- growth & development : Influenza A Virus, H7N9 Subtype, Reassortant Viruses.
- immunology : Influenza A Virus, H7N9 Subtype.
- prevention & control : Orthomyxoviridae Infections.
- Adaptation, Biological, Amino Acid Substitution, Animals, Chick Embryo, Disease Models, Animal, Dogs, Ferrets, Madin Darby Canine Kidney Cells, Survival Analysis, Virus Attachment, Virus Replication.
Abstract
The circulating avian influenza A(H7N9) has caused recurrent epidemic waves with high mortality in China since 2013, in which the alarming fifth wave crossing 2016 and 2017 was highlighted by a large number of human infections and the emergence of highly pathogenic avian influenza (HPAI) A(H7N9) strains in human cases. We generated low-pathogenic reassortant CVVs derived from the emerging A(H7N9) with improved virus replication and protein yield in both MDCK cells and eggs by introducing a single substitution, G218E, into HA, which was associated with reducing HA receptor binding and subsequently balancing HA-NA functions. The
Url:
DOI: 10.1128/JVI.00570-19
PubMed: 31270231
PubMed Central: 6744242
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<term>Animals</term>
<term>Chick Embryo</term>
<term>Disease Models, Animal</term>
<term>Dogs</term>
<term>Ferrets</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (genetics)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (metabolism)</term>
<term>Influenza A Virus, H7N9 Subtype (genetics)</term>
<term>Influenza A Virus, H7N9 Subtype (growth & development)</term>
<term>Influenza A Virus, H7N9 Subtype (immunology)</term>
<term>Influenza Vaccines (administration & dosage)</term>
<term>Influenza Vaccines (genetics)</term>
<term>Influenza Vaccines (immunology)</term>
<term>Madin Darby Canine Kidney Cells</term>
<term>Mutant Proteins (genetics)</term>
<term>Mutant Proteins (metabolism)</term>
<term>Orthomyxoviridae Infections (prevention & control)</term>
<term>Reassortant Viruses (genetics)</term>
<term>Reassortant Viruses (growth & development)</term>
<term>Survival Analysis</term>
<term>Vaccines, Attenuated (administration & dosage)</term>
<term>Vaccines, Attenuated (genetics)</term>
<term>Vaccines, Attenuated (immunology)</term>
<term>Virus Attachment</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adaptation biologique</term>
<term>Analyse de survie</term>
<term>Animaux</term>
<term>Attachement viral</term>
<term>Cellules rénales canines Madin-Darby</term>
<term>Chiens</term>
<term>Embryon de poulet</term>
<term>Furets</term>
<term>Glycoprotéine hémagglutinine du virus influenza (génétique)</term>
<term>Glycoprotéine hémagglutinine du virus influenza (métabolisme)</term>
<term>Infections à Orthomyxoviridae ()</term>
<term>Modèles animaux de maladie humaine</term>
<term>Protéines mutantes (génétique)</term>
<term>Protéines mutantes (métabolisme)</term>
<term>Réplication virale</term>
<term>Sous-type H7N9 du virus de la grippe A (croissance et développement)</term>
<term>Sous-type H7N9 du virus de la grippe A (génétique)</term>
<term>Sous-type H7N9 du virus de la grippe A (immunologie)</term>
<term>Substitution d'acide aminé</term>
<term>Vaccins antigrippaux (administration et posologie)</term>
<term>Vaccins antigrippaux (génétique)</term>
<term>Vaccins antigrippaux (immunologie)</term>
<term>Vaccins atténués (administration et posologie)</term>
<term>Vaccins atténués (génétique)</term>
<term>Vaccins atténués (immunologie)</term>
<term>Virus recombinants (croissance et développement)</term>
<term>Virus recombinants (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Influenza Vaccines</term>
<term>Vaccines, Attenuated</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Hemagglutinin Glycoproteins, Influenza Virus</term>
<term>Influenza Vaccines</term>
<term>Mutant Proteins</term>
<term>Vaccines, Attenuated</term>
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<term>Vaccines, Attenuated</term>
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<term>Mutant Proteins</term>
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<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Vaccins antigrippaux</term>
<term>Vaccins atténués</term>
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<keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Sous-type H7N9 du virus de la grippe A</term>
<term>Virus recombinants</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza A Virus, H7N9 Subtype</term>
<term>Reassortant Viruses</term>
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<keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Influenza A Virus, H7N9 Subtype</term>
<term>Reassortant Viruses</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéine hémagglutinine du virus influenza</term>
<term>Protéines mutantes</term>
<term>Sous-type H7N9 du virus de la grippe A</term>
<term>Vaccins antigrippaux</term>
<term>Vaccins atténués</term>
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<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Sous-type H7N9 du virus de la grippe A</term>
<term>Vaccins antigrippaux</term>
<term>Vaccins atténués</term>
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<term>Chick Embryo</term>
<term>Disease Models, Animal</term>
<term>Dogs</term>
<term>Ferrets</term>
<term>Madin Darby Canine Kidney Cells</term>
<term>Survival Analysis</term>
<term>Virus Attachment</term>
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<term>Analyse de survie</term>
<term>Animaux</term>
<term>Attachement viral</term>
<term>Cellules rénales canines Madin-Darby</term>
<term>Chiens</term>
<term>Embryon de poulet</term>
<term>Furets</term>
<term>Infections à Orthomyxoviridae</term>
<term>Modèles animaux de maladie humaine</term>
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<front><div type="abstract" xml:lang="en"><p>The circulating avian influenza A(H7N9) has caused recurrent epidemic waves with high mortality in China since 2013, in which the alarming fifth wave crossing 2016 and 2017 was highlighted by a large number of human infections and the emergence of highly pathogenic avian influenza (HPAI) A(H7N9) strains in human cases. We generated low-pathogenic reassortant CVVs derived from the emerging A(H7N9) with improved virus replication and protein yield in both MDCK cells and eggs by introducing a single substitution, G218E, into HA, which was associated with reducing HA receptor binding and subsequently balancing HA-NA functions. The <italic>in vitro</italic>
and <italic>in vivo</italic>
experiments demonstrated comparable antigenicity of the G218E CVVs with that of their wild-type (WT) counterparts, and both the WT and the G218E CVVs fully protected ferrets from parental HPAI virus challenge. With high yield traits and the anticipated antigenicity, the G218E CVVs should benefit preparedness against the threat of an A(H7N9) influenza pandemic.</p>
</div>
</front>
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<double pmid="31270231"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Single Amino Acid Substitution at Residue 218 of Hemagglutinin Improves the Growth of Influenza A(H7N9) Candidate Vaccine Viruses</title>
<author><name sortKey="Li, Xing" sort="Li, Xing" uniqKey="Li X" first="Xing" last="Li">Xing Li</name>
<affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gao, Yamei" sort="Gao, Yamei" uniqKey="Gao Y" first="Yamei" last="Gao">Yamei Gao</name>
<affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ye, Zhiping" sort="Ye, Zhiping" uniqKey="Ye Z" first="Zhiping" last="Ye">Zhiping Ye</name>
<affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">31270231</idno>
<idno type="pmc">6744242</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744242</idno>
<idno type="RBID">PMC:6744242</idno>
<idno type="doi">10.1128/JVI.00570-19</idno>
<date when="2019">2019</date>
<idno type="wicri:Area/Pmc/Corpus">000B54</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B54</idno>
<idno type="wicri:Area/Pmc/Curation">000B54</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000B54</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000105</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000105</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Single Amino Acid Substitution at Residue 218 of Hemagglutinin Improves the Growth of Influenza A(H7N9) Candidate Vaccine Viruses</title>
<author><name sortKey="Li, Xing" sort="Li, Xing" uniqKey="Li X" first="Xing" last="Li">Xing Li</name>
<affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
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<author><name sortKey="Gao, Yamei" sort="Gao, Yamei" uniqKey="Gao Y" first="Yamei" last="Gao">Yamei Gao</name>
<affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
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<author><name sortKey="Ye, Zhiping" sort="Ye, Zhiping" uniqKey="Ye Z" first="Zhiping" last="Ye">Zhiping Ye</name>
<affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
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</analytic>
<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
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<profileDesc><textClass></textClass>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><p>The circulating avian influenza A(H7N9) has caused recurrent epidemic waves with high mortality in China since 2013, in which the alarming fifth wave crossing 2016 and 2017 was highlighted by a large number of human infections and the emergence of highly pathogenic avian influenza (HPAI) A(H7N9) strains in human cases. We generated low-pathogenic reassortant CVVs derived from the emerging A(H7N9) with improved virus replication and protein yield in both MDCK cells and eggs by introducing a single substitution, G218E, into HA, which was associated with reducing HA receptor binding and subsequently balancing HA-NA functions. The <italic>in vitro</italic>
and <italic>in vivo</italic>
experiments demonstrated comparable antigenicity of the G218E CVVs with that of their wild-type (WT) counterparts, and both the WT and the G218E CVVs fully protected ferrets from parental HPAI virus challenge. With high yield traits and the anticipated antigenicity, the G218E CVVs should benefit preparedness against the threat of an A(H7N9) influenza pandemic.</p>
</div>
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<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Single Amino Acid Substitution at Residue 218 of Hemagglutinin Improves the Growth of Influenza A(H7N9) Candidate Vaccine Viruses.</title>
<author><name sortKey="Li, Xing" sort="Li, Xing" uniqKey="Li X" first="Xing" last="Li">Xing Li</name>
<affiliation><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA xing.li@fda.hhs.gov Zhiping.ye@fda.hhs.gov.</nlm:affiliation>
<wicri:noCountry code="subField">USA xing.li@fda.hhs.gov</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Gao, Yamei" sort="Gao, Yamei" uniqKey="Gao Y" first="Yamei" last="Gao">Yamei Gao</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland</wicri:regionArea>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Ye, Zhiping" sort="Ye, Zhiping" uniqKey="Ye Z" first="Zhiping" last="Ye">Zhiping Ye</name>
<affiliation><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA xing.li@fda.hhs.gov Zhiping.ye@fda.hhs.gov.</nlm:affiliation>
<wicri:noCountry code="subField">USA xing.li@fda.hhs.gov</wicri:noCountry>
</affiliation>
</author>
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<idno type="pmid">31270231</idno>
<idno type="doi">10.1128/JVI.00570-19</idno>
<idno type="wicri:Area/PubMed/Corpus">000120</idno>
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<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000190</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">A Single Amino Acid Substitution at Residue 218 of Hemagglutinin Improves the Growth of Influenza A(H7N9) Candidate Vaccine Viruses.</title>
<author><name sortKey="Li, Xing" sort="Li, Xing" uniqKey="Li X" first="Xing" last="Li">Xing Li</name>
<affiliation><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA xing.li@fda.hhs.gov Zhiping.ye@fda.hhs.gov.</nlm:affiliation>
<wicri:noCountry code="subField">USA xing.li@fda.hhs.gov</wicri:noCountry>
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<affiliation wicri:level="2"><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland</wicri:regionArea>
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</author>
<author><name sortKey="Ye, Zhiping" sort="Ye, Zhiping" uniqKey="Ye Z" first="Zhiping" last="Ye">Zhiping Ye</name>
<affiliation><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA xing.li@fda.hhs.gov Zhiping.ye@fda.hhs.gov.</nlm:affiliation>
<wicri:noCountry code="subField">USA xing.li@fda.hhs.gov</wicri:noCountry>
</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>
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<term>Amino Acid Substitution</term>
<term>Animals</term>
<term>Chick Embryo</term>
<term>Disease Models, Animal</term>
<term>Dogs</term>
<term>Ferrets</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (genetics)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (metabolism)</term>
<term>Influenza A Virus, H7N9 Subtype (genetics)</term>
<term>Influenza A Virus, H7N9 Subtype (growth & development)</term>
<term>Influenza A Virus, H7N9 Subtype (immunology)</term>
<term>Influenza Vaccines (administration & dosage)</term>
<term>Influenza Vaccines (genetics)</term>
<term>Influenza Vaccines (immunology)</term>
<term>Madin Darby Canine Kidney Cells</term>
<term>Mutant Proteins (genetics)</term>
<term>Mutant Proteins (metabolism)</term>
<term>Orthomyxoviridae Infections (prevention & control)</term>
<term>Reassortant Viruses (genetics)</term>
<term>Reassortant Viruses (growth & development)</term>
<term>Survival Analysis</term>
<term>Vaccines, Attenuated (administration & dosage)</term>
<term>Vaccines, Attenuated (genetics)</term>
<term>Vaccines, Attenuated (immunology)</term>
<term>Virus Attachment</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adaptation biologique</term>
<term>Analyse de survie</term>
<term>Animaux</term>
<term>Attachement viral</term>
<term>Cellules rénales canines Madin-Darby</term>
<term>Chiens</term>
<term>Embryon de poulet</term>
<term>Furets</term>
<term>Glycoprotéine hémagglutinine du virus influenza (génétique)</term>
<term>Glycoprotéine hémagglutinine du virus influenza (métabolisme)</term>
<term>Infections à Orthomyxoviridae ()</term>
<term>Modèles animaux de maladie humaine</term>
<term>Protéines mutantes (génétique)</term>
<term>Protéines mutantes (métabolisme)</term>
<term>Réplication virale</term>
<term>Sous-type H7N9 du virus de la grippe A (croissance et développement)</term>
<term>Sous-type H7N9 du virus de la grippe A (génétique)</term>
<term>Sous-type H7N9 du virus de la grippe A (immunologie)</term>
<term>Substitution d'acide aminé</term>
<term>Vaccins antigrippaux (administration et posologie)</term>
<term>Vaccins antigrippaux (génétique)</term>
<term>Vaccins antigrippaux (immunologie)</term>
<term>Vaccins atténués (administration et posologie)</term>
<term>Vaccins atténués (génétique)</term>
<term>Vaccins atténués (immunologie)</term>
<term>Virus recombinants (croissance et développement)</term>
<term>Virus recombinants (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Influenza Vaccines</term>
<term>Vaccines, Attenuated</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Hemagglutinin Glycoproteins, Influenza Virus</term>
<term>Influenza Vaccines</term>
<term>Mutant Proteins</term>
<term>Vaccines, Attenuated</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Influenza Vaccines</term>
<term>Vaccines, Attenuated</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Hemagglutinin Glycoproteins, Influenza Virus</term>
<term>Mutant Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Vaccins antigrippaux</term>
<term>Vaccins atténués</term>
</keywords>
<keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Sous-type H7N9 du virus de la grippe A</term>
<term>Virus recombinants</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza A Virus, H7N9 Subtype</term>
<term>Reassortant Viruses</term>
</keywords>
<keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Influenza A Virus, H7N9 Subtype</term>
<term>Reassortant Viruses</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéine hémagglutinine du virus influenza</term>
<term>Protéines mutantes</term>
<term>Sous-type H7N9 du virus de la grippe A</term>
<term>Vaccins antigrippaux</term>
<term>Vaccins atténués</term>
<term>Virus recombinants</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Sous-type H7N9 du virus de la grippe A</term>
<term>Vaccins antigrippaux</term>
<term>Vaccins atténués</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Influenza A Virus, H7N9 Subtype</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glycoprotéine hémagglutinine du virus influenza</term>
<term>Protéines mutantes</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Orthomyxoviridae Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adaptation, Biological</term>
<term>Amino Acid Substitution</term>
<term>Animals</term>
<term>Chick Embryo</term>
<term>Disease Models, Animal</term>
<term>Dogs</term>
<term>Ferrets</term>
<term>Madin Darby Canine Kidney Cells</term>
<term>Survival Analysis</term>
<term>Virus Attachment</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adaptation biologique</term>
<term>Analyse de survie</term>
<term>Animaux</term>
<term>Attachement viral</term>
<term>Cellules rénales canines Madin-Darby</term>
<term>Chiens</term>
<term>Embryon de poulet</term>
<term>Furets</term>
<term>Infections à Orthomyxoviridae</term>
<term>Modèles animaux de maladie humaine</term>
<term>Réplication virale</term>
<term>Substitution d'acide aminé</term>
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<front><div type="abstract" xml:lang="en">The potential avian influenza pandemic remains a threat to public health, as the avian-origin influenza A(H7N9) virus has caused more than 1,560 laboratory-confirmed human infections since 2013, with nearly 40% mortality. Development of low-pathogenic candidate vaccine viruses (CVVs) for vaccine production is essential for pandemic preparedness. However, the suboptimal growth of CVVs in mammalian cells and chicken eggs is often a challenge. By introducing a single adaptive substitution, G218E, into the hemagglutinin (HA), we generated reassortant A(H7N9)-G218E CVVs that were characterized by significantly enhanced growth in both cells and eggs. These G218E CVVs retained the original antigenicity, as determined by a hemagglutination inhibition assay, and effectively protected ferrets from lethal challenge with the highly pathogenic parental virus. We found that the suboptimal replication of the parental H7 CVVs was associated with impeded progeny virus release as a result of strong HA receptor binding relative to weak neuraminidase (NA) cleavage of receptors. In contrast, the G218E-mediated growth improvement was attributed to relatively balanced HA and NA functions, resulted from reduced HA binding to both human- and avian-type receptors, and thus facilitated NA-mediated virus release. Our findings revealed that a single amino acid mutation at residue 218 of the HA improved the growth of A(H7N9) influenza virus by balancing HA and NA functions, shedding light on an alternative approach for optimizing certain influenza CVVs.<b>IMPORTANCE</b>
The circulating avian influenza A(H7N9) has caused recurrent epidemic waves with high mortality in China since 2013, in which the alarming fifth wave crossing 2016 and 2017 was highlighted by a large number of human infections and the emergence of highly pathogenic avian influenza (HPAI) A(H7N9) strains in human cases. We generated low-pathogenic reassortant CVVs derived from the emerging A(H7N9) with improved virus replication and protein yield in both MDCK cells and eggs by introducing a single substitution, G218E, into HA, which was associated with reducing HA receptor binding and subsequently balancing HA-NA functions. The <i>in vitro</i>
and <i>in vivo</i>
experiments demonstrated comparable antigenicity of the G218E CVVs with that of their wild-type (WT) counterparts, and both the WT and the G218E CVVs fully protected ferrets from parental HPAI virus challenge. With high yield traits and the anticipated antigenicity, the G218E CVVs should benefit preparedness against the threat of an A(H7N9) influenza pandemic.</div>
</front>
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