The 2nd sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance
Identifieur interne : 000005 ( 1957/Analysis ); précédent : 000004; suivant : 000006The 2nd sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance
Auteurs : Wenjuan Du [Pays-Bas] ; Hongbo Guo [Pays-Bas] ; Vera S. Nijman [Pays-Bas] ; Jennifer Doedt [Allemagne] ; Erhard Van Der Vries [Pays-Bas] ; Joline Van Der Lee [Pays-Bas] ; Zeshi Li [Pays-Bas] ; Geert-Jan Boons [Pays-Bas] ; Frank J. M. Van Kuppeveld [Pays-Bas] ; Erik De Vries [Pays-Bas] ; Mikhail Matrosovich [Allemagne] ; Cornelis A. M. De Haan [Pays-Bas]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2019.
Descripteurs français
- KwdFr :
- Acide N-acétyl-neuraminique (génétique), Acide N-acétyl-neuraminique (métabolisme), Animaux, Cellules Vero, Cellules rénales canines Madin-Darby, Chiens, Humains, Protéines virales (), Protéines virales (génétique), Protéines virales (métabolisme), Récepteurs viraux (), Récepteurs viraux (génétique), Récepteurs viraux (métabolisme), Sialidase (), Sialidase (génétique), Sialidase (métabolisme), Sites de fixation, Sous-type H2N2 du virus de la grippe A (), Sous-type H2N2 du virus de la grippe A (génétique), Sous-type H2N2 du virus de la grippe A (métabolisme), Sous-type H3N2 du virus de la grippe A (), Sous-type H3N2 du virus de la grippe A (génétique), Sous-type H3N2 du virus de la grippe A (métabolisme), Virion (), Virion (génétique), Virion (métabolisme).
- MESH :
- génétique : Acide N-acétyl-neuraminique, Protéines virales, Récepteurs viraux, Sialidase, Sous-type H2N2 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A, Virion.
- métabolisme : Acide N-acétyl-neuraminique, Protéines virales, Récepteurs viraux, Sialidase, Sous-type H2N2 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A, Virion.
- Animaux, Cellules Vero, Cellules rénales canines Madin-Darby, Chiens, Humains, Protéines virales, Récepteurs viraux, Sialidase, Sites de fixation, Sous-type H2N2 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A, Virion.
English descriptors
- KwdEn :
- Animals, Binding Sites, Chlorocebus aethiops, Dogs, Humans, Influenza A Virus, H2N2 Subtype (chemistry), Influenza A Virus, H2N2 Subtype (genetics), Influenza A Virus, H2N2 Subtype (metabolism), Influenza A Virus, H3N2 Subtype (chemistry), Influenza A Virus, H3N2 Subtype (genetics), Influenza A Virus, H3N2 Subtype (metabolism), Madin Darby Canine Kidney Cells, N-Acetylneuraminic Acid (genetics), N-Acetylneuraminic Acid (metabolism), Neuraminidase (chemistry), Neuraminidase (genetics), Neuraminidase (metabolism), Receptors, Virus (chemistry), Receptors, Virus (genetics), Receptors, Virus (metabolism), Vero Cells, Viral Proteins (chemistry), Viral Proteins (genetics), Viral Proteins (metabolism), Virion (chemistry), Virion (genetics), Virion (metabolism).
- MESH :
- chemical , chemistry : Neuraminidase, Receptors, Virus, Viral Proteins.
- chemical , genetics : N-Acetylneuraminic Acid, Neuraminidase, Receptors, Virus, Viral Proteins.
- chemistry : Influenza A Virus, H2N2 Subtype, Influenza A Virus, H3N2 Subtype, Virion.
- genetics : Influenza A Virus, H2N2 Subtype, Influenza A Virus, H3N2 Subtype, Virion.
- metabolism : Influenza A Virus, H2N2 Subtype, Influenza A Virus, H3N2 Subtype, N-Acetylneuraminic Acid, Neuraminidase, Receptors, Virus, Viral Proteins, Virion.
- Animals, Binding Sites, Chlorocebus aethiops, Dogs, Humans, Madin Darby Canine Kidney Cells, Vero Cells.
Abstract
Influenza A virus (IAV) neuraminidase (NA) receptor-destroying activity and hemagglutinin (HA) receptor-binding affinity need to be balanced with the host receptor repertoire for optimal viral fitness. NAs of avian, but not human viruses, contain a functional 2nd sialic acid (SIA)-binding site (2SBS) adjacent to the catalytic site, which contributes to sialidase activity against multivalent substrates. The receptor-binding specificity and potentially crucial contribution of the 2SBS to the HA-NA balance of virus particles is, however, poorly characterized. Here, we elucidated the receptor-binding specificity of the 2SBS of N2 NA and established an important role for this site in the virion HA-NA-receptor balance. NAs of H2N2/1957 pandemic virus with or without a functional 2SBS and viruses containing this NA were analysed. Avian-like N2, with a restored 2SBS due to an amino acid substitution at position 367, was more active than human N2 on multivalent substrates containing α2,3-linked SIAs, corresponding with the pronounced binding-specificity of avian-like N2 for these receptors. When introduced into human viruses, avian-like N2 gave rise to altered plaque morphology and decreased replication compared to human N2. An opposite replication phenotype was observed when N2 was combined with avian-like HA. Specific bio-layer interferometry assays revealed a clear effect of the 2SBS on the dynamic interaction of virus particles with receptors. The absence or presence of a functional 2SBS affected virion-receptor binding and receptor cleavage required for particle movement on a receptor-coated surface and subsequent NA-dependent self-elution. The contribution of the 2SBS to virus-receptor interactions depended on the receptor-binding properties of HA and the identity of the receptors used. We conclude that the 2SBS is an important and underappreciated determinant of the HA-NA-receptor balance. The rapid loss of a functional 2SBS in pandemic viruses may have served to balance the novel host receptor-repertoire and altered receptor-binding properties of the corresponding HA protein.
Url:
DOI: 10.1371/journal.ppat.1007860
PubMed: 31181126
PubMed Central: 6586374
Affiliations:
- Allemagne, Pays-Bas
- District de Giessen, Hesse (Land), Utrecht (province)
- Marbourg, Utrecht
- Université d'Utrecht
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000B94
- to stream Pmc, to step Curation: 000B94
- to stream Pmc, to step Checkpoint: 000025
- to stream PubMed, to step Corpus: 000008
- to stream PubMed, to step Curation: 000008
- to stream PubMed, to step Checkpoint: 000007
- to stream Ncbi, to step Merge: 000F88
- to stream Ncbi, to step Curation: 000F88
- to stream Ncbi, to step Checkpoint: 000F88
- to stream Main, to step Merge: 000044
- to stream Main, to step Curation: 000044
- to stream Main, to step Exploration: 000044
- to stream 1957, to step Extraction: 000005
Links to Exploration step
PMC:6586374Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The 2<sup>nd</sup> sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance</title><author><name sortKey="Du, Wenjuan" sort="Du, Wenjuan" uniqKey="Du W" first="Wenjuan" last="Du">Wenjuan Du</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Guo, Hongbo" sort="Guo, Hongbo" uniqKey="Guo H" first="Hongbo" last="Guo">Hongbo Guo</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Nijman, Vera S" sort="Nijman, Vera S" uniqKey="Nijman V" first="Vera S." last="Nijman">Vera S. Nijman</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Doedt, Jennifer" sort="Doedt, Jennifer" uniqKey="Doedt J" first="Jennifer" last="Doedt">Jennifer Doedt</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Institute of Virology, Philipps University, Marburg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Philipps University, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="Van Der Vries, Erhard" sort="Van Der Vries, Erhard" uniqKey="Van Der Vries E" first="Erhard" last="Van Der Vries">Erhard Van Der Vries</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Van Der Lee, Joline" sort="Van Der Lee, Joline" uniqKey="Van Der Lee J" first="Joline" last="Van Der Lee">Joline Van Der Lee</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Li, Zeshi" sort="Li, Zeshi" uniqKey="Li Z" first="Zeshi" last="Li">Zeshi Li</name><affiliation wicri:level="4"><nlm:aff id="aff003"><addr-line>Department of Chemical Biology and Drug Discovery, Utrecht University, Utrecht, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Chemical Biology and Drug Discovery, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Boons, Geert Jan" sort="Boons, Geert Jan" uniqKey="Boons G" first="Geert-Jan" last="Boons">Geert-Jan Boons</name><affiliation wicri:level="4"><nlm:aff id="aff003"><addr-line>Department of Chemical Biology and Drug Discovery, Utrecht University, Utrecht, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Chemical Biology and Drug Discovery, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Van Kuppeveld, Frank J M" sort="Van Kuppeveld, Frank J M" uniqKey="Van Kuppeveld F" first="Frank J. M." last="Van Kuppeveld">Frank J. M. Van Kuppeveld</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="De Vries, Erik" sort="De Vries, Erik" uniqKey="De Vries E" first="Erik" last="De Vries">Erik De Vries</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Matrosovich, Mikhail" sort="Matrosovich, Mikhail" uniqKey="Matrosovich M" first="Mikhail" last="Matrosovich">Mikhail Matrosovich</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Institute of Virology, Philipps University, Marburg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Philipps University, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="De Haan, Cornelis A M" sort="De Haan, Cornelis A M" uniqKey="De Haan C" first="Cornelis A. M." last="De Haan">Cornelis A. M. De Haan</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31181126</idno><idno type="pmc">6586374</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586374</idno><idno type="RBID">PMC:6586374</idno><idno type="doi">10.1371/journal.ppat.1007860</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000B94</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B94</idno><idno type="wicri:Area/Pmc/Curation">000B94</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000B94</idno><idno type="wicri:Area/Pmc/Checkpoint">000025</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000025</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:31181126</idno><idno type="wicri:Area/PubMed/Corpus">000008</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000008</idno><idno type="wicri:Area/PubMed/Curation">000008</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000008</idno><idno type="wicri:Area/PubMed/Checkpoint">000007</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000007</idno><idno type="wicri:Area/Ncbi/Merge">000F88</idno><idno type="wicri:Area/Ncbi/Curation">000F88</idno><idno type="wicri:Area/Ncbi/Checkpoint">000F88</idno><idno type="wicri:Area/Main/Merge">000044</idno><idno type="wicri:Area/Main/Curation">000044</idno><idno type="wicri:Area/Main/Exploration">000044</idno><idno type="wicri:Area/1957/Extraction">000005</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The 2<sup>nd</sup> sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance</title><author><name sortKey="Du, Wenjuan" sort="Du, Wenjuan" uniqKey="Du W" first="Wenjuan" last="Du">Wenjuan Du</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Guo, Hongbo" sort="Guo, Hongbo" uniqKey="Guo H" first="Hongbo" last="Guo">Hongbo Guo</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Nijman, Vera S" sort="Nijman, Vera S" uniqKey="Nijman V" first="Vera S." last="Nijman">Vera S. Nijman</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Doedt, Jennifer" sort="Doedt, Jennifer" uniqKey="Doedt J" first="Jennifer" last="Doedt">Jennifer Doedt</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Institute of Virology, Philipps University, Marburg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Philipps University, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="Van Der Vries, Erhard" sort="Van Der Vries, Erhard" uniqKey="Van Der Vries E" first="Erhard" last="Van Der Vries">Erhard Van Der Vries</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Van Der Lee, Joline" sort="Van Der Lee, Joline" uniqKey="Van Der Lee J" first="Joline" last="Van Der Lee">Joline Van Der Lee</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Li, Zeshi" sort="Li, Zeshi" uniqKey="Li Z" first="Zeshi" last="Li">Zeshi Li</name><affiliation wicri:level="4"><nlm:aff id="aff003"><addr-line>Department of Chemical Biology and Drug Discovery, Utrecht University, Utrecht, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Chemical Biology and Drug Discovery, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Boons, Geert Jan" sort="Boons, Geert Jan" uniqKey="Boons G" first="Geert-Jan" last="Boons">Geert-Jan Boons</name><affiliation wicri:level="4"><nlm:aff id="aff003"><addr-line>Department of Chemical Biology and Drug Discovery, Utrecht University, Utrecht, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Chemical Biology and Drug Discovery, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Van Kuppeveld, Frank J M" sort="Van Kuppeveld, Frank J M" uniqKey="Van Kuppeveld F" first="Frank J. M." last="Van Kuppeveld">Frank J. M. Van Kuppeveld</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="De Vries, Erik" sort="De Vries, Erik" uniqKey="De Vries E" first="Erik" last="De Vries">Erik De Vries</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Matrosovich, Mikhail" sort="Matrosovich, Mikhail" uniqKey="Matrosovich M" first="Mikhail" last="Matrosovich">Mikhail Matrosovich</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Institute of Virology, Philipps University, Marburg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Philipps University, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="De Haan, Cornelis A M" sort="De Haan, Cornelis A M" uniqKey="De Haan C" first="Cornelis A. M." last="De Haan">Cornelis A. M. De Haan</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Binding Sites</term><term>Chlorocebus aethiops</term><term>Dogs</term><term>Humans</term><term>Influenza A Virus, H2N2 Subtype (chemistry)</term><term>Influenza A Virus, H2N2 Subtype (genetics)</term><term>Influenza A Virus, H2N2 Subtype (metabolism)</term><term>Influenza A Virus, H3N2 Subtype (chemistry)</term><term>Influenza A Virus, H3N2 Subtype (genetics)</term><term>Influenza A Virus, H3N2 Subtype (metabolism)</term><term>Madin Darby Canine Kidney Cells</term><term>N-Acetylneuraminic Acid (genetics)</term><term>N-Acetylneuraminic Acid (metabolism)</term><term>Neuraminidase (chemistry)</term><term>Neuraminidase (genetics)</term><term>Neuraminidase (metabolism)</term><term>Receptors, Virus (chemistry)</term><term>Receptors, Virus (genetics)</term><term>Receptors, Virus (metabolism)</term><term>Vero Cells</term><term>Viral Proteins (chemistry)</term><term>Viral Proteins (genetics)</term><term>Viral Proteins (metabolism)</term><term>Virion (chemistry)</term><term>Virion (genetics)</term><term>Virion (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acide N-acétyl-neuraminique (génétique)</term><term>Acide N-acétyl-neuraminique (métabolisme)</term><term>Animaux</term><term>Cellules Vero</term><term>Cellules rénales canines Madin-Darby</term><term>Chiens</term><term>Humains</term><term>Protéines virales ()</term><term>Protéines virales (génétique)</term><term>Protéines virales (métabolisme)</term><term>Récepteurs viraux ()</term><term>Récepteurs viraux (génétique)</term><term>Récepteurs viraux (métabolisme)</term><term>Sialidase ()</term><term>Sialidase (génétique)</term><term>Sialidase (métabolisme)</term><term>Sites de fixation</term><term>Sous-type H2N2 du virus de la grippe A ()</term><term>Sous-type H2N2 du virus de la grippe A (génétique)</term><term>Sous-type H2N2 du virus de la grippe A (métabolisme)</term><term>Sous-type H3N2 du virus de la grippe A ()</term><term>Sous-type H3N2 du virus de la grippe A (génétique)</term><term>Sous-type H3N2 du virus de la grippe A (métabolisme)</term><term>Virion ()</term><term>Virion (génétique)</term><term>Virion (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Neuraminidase</term><term>Receptors, Virus</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>N-Acetylneuraminic Acid</term><term>Neuraminidase</term><term>Receptors, Virus</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Influenza A Virus, H2N2 Subtype</term><term>Influenza A Virus, H3N2 Subtype</term><term>Virion</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza A Virus, H2N2 Subtype</term><term>Influenza A Virus, H3N2 Subtype</term><term>Virion</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Acide N-acétyl-neuraminique</term><term>Protéines virales</term><term>Récepteurs viraux</term><term>Sialidase</term><term>Sous-type H2N2 du virus de la grippe A</term><term>Sous-type H3N2 du virus de la grippe A</term><term>Virion</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Influenza A Virus, H2N2 Subtype</term><term>Influenza A Virus, H3N2 Subtype</term><term>N-Acetylneuraminic Acid</term><term>Neuraminidase</term><term>Receptors, Virus</term><term>Viral Proteins</term><term>Virion</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Acide N-acétyl-neuraminique</term><term>Protéines virales</term><term>Récepteurs viraux</term><term>Sialidase</term><term>Sous-type H2N2 du virus de la grippe A</term><term>Sous-type H3N2 du virus de la grippe A</term><term>Virion</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Binding Sites</term><term>Chlorocebus aethiops</term><term>Dogs</term><term>Humans</term><term>Madin Darby Canine Kidney Cells</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Cellules rénales canines Madin-Darby</term><term>Chiens</term><term>Humains</term><term>Protéines virales</term><term>Récepteurs viraux</term><term>Sialidase</term><term>Sites de fixation</term><term>Sous-type H2N2 du virus de la grippe A</term><term>Sous-type H3N2 du virus de la grippe A</term><term>Virion</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Influenza A virus (IAV) neuraminidase (NA) receptor-destroying activity and hemagglutinin (HA) receptor-binding affinity need to be balanced with the host receptor repertoire for optimal viral fitness. NAs of avian, but not human viruses, contain a functional 2<sup>nd</sup> sialic acid (SIA)-binding site (2SBS) adjacent to the catalytic site, which contributes to sialidase activity against multivalent substrates. The receptor-binding specificity and potentially crucial contribution of the 2SBS to the HA-NA balance of virus particles is, however, poorly characterized. Here, we elucidated the receptor-binding specificity of the 2SBS of N2 NA and established an important role for this site in the virion HA-NA-receptor balance. NAs of H2N2/1957 pandemic virus with or without a functional 2SBS and viruses containing this NA were analysed. Avian-like N2, with a restored 2SBS due to an amino acid substitution at position 367, was more active than human N2 on multivalent substrates containing α2,3-linked SIAs, corresponding with the pronounced binding-specificity of avian-like N2 for these receptors. When introduced into human viruses, avian-like N2 gave rise to altered plaque morphology and decreased replication compared to human N2. An opposite replication phenotype was observed when N2 was combined with avian-like HA. Specific bio-layer interferometry assays revealed a clear effect of the 2SBS on the dynamic interaction of virus particles with receptors. The absence or presence of a functional 2SBS affected virion-receptor binding and receptor cleavage required for particle movement on a receptor-coated surface and subsequent NA-dependent self-elution. The contribution of the 2SBS to virus-receptor interactions depended on the receptor-binding properties of HA and the identity of the receptors used. We conclude that the 2SBS is an important and underappreciated determinant of the HA-NA-receptor balance. The rapid loss of a functional 2SBS in pandemic viruses may have served to balance the novel host receptor-repertoire and altered receptor-binding properties of the corresponding HA protein.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Gambaryan, As" uniqKey="Gambaryan A">AS Gambaryan</name></author><author><name sortKey="Matrosovich, Mn" uniqKey="Matrosovich M">MN Matrosovich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Byrd Leotis, L" uniqKey="Byrd Leotis L">L Byrd-Leotis</name></author><author><name sortKey="Cummings, Rd" uniqKey="Cummings R">RD Cummings</name></author><author><name sortKey="Steinhauer, Da" uniqKey="Steinhauer D">DA Steinhauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gaymard, A" uniqKey="Gaymard A">A Gaymard</name></author><author><name sortKey="Le Briand, N" uniqKey="Le Briand N">N Le Briand</name></author><author><name sortKey="Frobert, E" uniqKey="Frobert E">E Frobert</name></author><author><name sortKey="Lina, B" uniqKey="Lina B">B Lina</name></author><author><name sortKey="Escuret, V" uniqKey="Escuret V">V Escuret</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yen, Hl" uniqKey="Yen H">HL Yen</name></author><author><name sortKey="Liang, Ch" uniqKey="Liang C">CH Liang</name></author><author><name sortKey="Wu, Cy" uniqKey="Wu C">CY Wu</name></author><author><name sortKey="Forrest, Hl" uniqKey="Forrest H">HL Forrest</name></author><author><name sortKey="Ferguson, A" uniqKey="Ferguson A">A Ferguson</name></author><author><name sortKey="Choy, Kt" uniqKey="Choy K">KT Choy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, R" uniqKey="Xu R">R Xu</name></author><author><name sortKey="Zhu, X" uniqKey="Zhu X">X Zhu</name></author><author><name sortKey="Mcbride, R" uniqKey="Mcbride R">R McBride</name></author><author><name sortKey="Nycholat, Cm" uniqKey="Nycholat C">CM Nycholat</name></author><author><name sortKey="Yu, W" uniqKey="Yu W">W Yu</name></author><author><name sortKey="Paulson, Jc" uniqKey="Paulson J">JC Paulson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baigent, Sj" uniqKey="Baigent S">SJ Baigent</name></author><author><name sortKey="Mccauley, Jw" uniqKey="Mccauley J">JW McCauley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cohen, M" uniqKey="Cohen M">M Cohen</name></author><author><name sortKey="Zhang, X Q" uniqKey="Zhang X">X-Q Zhang</name></author><author><name sortKey="Senaati, Hp" uniqKey="Senaati H">HP Senaati</name></author><author><name sortKey="Chen, H W" uniqKey="Chen H">H-W Chen</name></author><author><name sortKey="Varki, Nm" uniqKey="Varki N">NM Varki</name></author><author><name sortKey="Schooley, Rt" uniqKey="Schooley R">RT Schooley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ito, T" uniqKey="Ito T">T Ito</name></author><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y Kawaoka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Russell, Rj" uniqKey="Russell R">RJ Russell</name></author><author><name sortKey="Stevens, Dj" uniqKey="Stevens D">DJ Stevens</name></author><author><name sortKey="Haire, Lf" uniqKey="Haire L">LF Haire</name></author><author><name sortKey="Gamblin, Sj" uniqKey="Gamblin S">SJ Gamblin</name></author><author><name sortKey="Skehel, Jj" uniqKey="Skehel J">JJ Skehel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Connor, Rj" uniqKey="Connor R">RJ Connor</name></author><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y Kawaoka</name></author><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author><author><name sortKey="Paulson, Jc" uniqKey="Paulson J">JC Paulson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matrosovich, M" uniqKey="Matrosovich M">M Matrosovich</name></author><author><name sortKey="Tuzikov, A" uniqKey="Tuzikov A">A Tuzikov</name></author><author><name sortKey="Bovin, N" uniqKey="Bovin N">N Bovin</name></author><author><name sortKey="Gambaryan, A" uniqKey="Gambaryan A">A Gambaryan</name></author><author><name sortKey="Klimov, A" uniqKey="Klimov A">A Klimov</name></author><author><name sortKey="Castrucci, Mr" uniqKey="Castrucci M">MR Castrucci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stevens, J" uniqKey="Stevens J">J Stevens</name></author><author><name sortKey="Blixt, O" uniqKey="Blixt O">O Blixt</name></author><author><name sortKey="Glaser, L" uniqKey="Glaser L">L Glaser</name></author><author><name sortKey="Taubenberger, Jk" uniqKey="Taubenberger J">JK Taubenberger</name></author><author><name sortKey="Palese, P" uniqKey="Palese P">P Palese</name></author><author><name sortKey="Paulson, Jc" uniqKey="Paulson J">JC Paulson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wasik, Br" uniqKey="Wasik B">BR Wasik</name></author><author><name sortKey="Barnard, Kn" uniqKey="Barnard K">KN Barnard</name></author><author><name sortKey="Parrish, Cr" uniqKey="Parrish C">CR Parrish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peng, W" uniqKey="Peng W">W Peng</name></author><author><name sortKey="De Vries, Rp" uniqKey="De Vries R">RP de Vries</name></author><author><name sortKey="Grant, Oc" uniqKey="Grant O">OC Grant</name></author><author><name sortKey="Thompson, Aj" uniqKey="Thompson A">AJ Thompson</name></author><author><name sortKey="Mcbride, R" uniqKey="Mcbride R">R McBride</name></author><author><name sortKey="Tsogtbaatar, B" uniqKey="Tsogtbaatar B">B Tsogtbaatar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Vries, Rp" uniqKey="De Vries R">RP de Vries</name></author><author><name sortKey="De Vries, E" uniqKey="De Vries E">E de Vries</name></author><author><name sortKey="Moore, Ks" uniqKey="Moore K">KS Moore</name></author><author><name sortKey="Rigter, A" uniqKey="Rigter A">A Rigter</name></author><author><name sortKey="Rottier, Pj" uniqKey="Rottier P">PJ Rottier</name></author><author><name sortKey="De Haan, Ca" uniqKey="De Haan C">CA de Haan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guo, H" uniqKey="Guo H">H Guo</name></author><author><name sortKey="De Vries, E" uniqKey="De Vries E">E de Vries</name></author><author><name sortKey="Mcbride, R" uniqKey="Mcbride R">R McBride</name></author><author><name sortKey="Dekkers, J" uniqKey="Dekkers J">J Dekkers</name></author><author><name sortKey="Peng, W" uniqKey="Peng W">W Peng</name></author><author><name sortKey="Bouwman, Km" uniqKey="Bouwman K">KM Bouwman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gambaryan, A" uniqKey="Gambaryan A">A Gambaryan</name></author><author><name sortKey="Yamnikova, S" uniqKey="Yamnikova S">S Yamnikova</name></author><author><name sortKey="Lvov, D" uniqKey="Lvov D">D Lvov</name></author><author><name sortKey="Tuzikov, A" uniqKey="Tuzikov A">A Tuzikov</name></author><author><name sortKey="Chinarev, A" uniqKey="Chinarev A">A Chinarev</name></author><author><name sortKey="Pazynina, G" uniqKey="Pazynina G">G Pazynina</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tumpey, Tm" uniqKey="Tumpey T">TM Tumpey</name></author><author><name sortKey="Maines, Tr" uniqKey="Maines T">TR Maines</name></author><author><name sortKey="Van Hoeven, N" uniqKey="Van Hoeven N">N Van Hoeven</name></author><author><name sortKey="Glaser, L" uniqKey="Glaser L">L Glaser</name></author><author><name sortKey="Sol Rzano, A" uniqKey="Sol Rzano A">A Solórzano</name></author><author><name sortKey="Pappas, C" uniqKey="Pappas C">C Pappas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saito, T" uniqKey="Saito T">T Saito</name></author><author><name sortKey="Taylor, G" uniqKey="Taylor G">G Taylor</name></author><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dai, M" uniqKey="Dai M">M Dai</name></author><author><name sortKey="Guo, H" uniqKey="Guo H">H Guo</name></author><author><name sortKey="Dortmans, Jc" uniqKey="Dortmans J">JC Dortmans</name></author><author><name sortKey="Dekkers, J" uniqKey="Dekkers J">J Dekkers</name></author><author><name sortKey="Nordholm, J" uniqKey="Nordholm J">J Nordholm</name></author><author><name sortKey="Daniels, R" uniqKey="Daniels R">R Daniels</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shtyrya, Ya" uniqKey="Shtyrya Y">YA Shtyrya</name></author><author><name sortKey="Mochalova, Lv" uniqKey="Mochalova L">LV Mochalova</name></author><author><name sortKey="Bovin, Nv" uniqKey="Bovin N">NV Bovin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Air, Gm" uniqKey="Air G">GM Air</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Russell, Rj" uniqKey="Russell R">RJ Russell</name></author><author><name sortKey="Haire, Lf" uniqKey="Haire L">LF Haire</name></author><author><name sortKey="Stevens, Dj" uniqKey="Stevens D">DJ Stevens</name></author><author><name sortKey="Collins, Pj" uniqKey="Collins P">PJ Collins</name></author><author><name sortKey="Lin, Yp" uniqKey="Lin Y">YP Lin</name></author><author><name sortKey="Blackburn, Gm" uniqKey="Blackburn G">GM Blackburn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baum, Lg" uniqKey="Baum L">LG Baum</name></author><author><name sortKey="Paulson, Jc" uniqKey="Paulson J">JC Paulson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Cao, H" uniqKey="Cao H">H Cao</name></author><author><name sortKey="Dao, N" uniqKey="Dao N">N Dao</name></author><author><name sortKey="Luo, Z" uniqKey="Luo Z">Z Luo</name></author><author><name sortKey="Yu, H" uniqKey="Yu H">H Yu</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, W" uniqKey="Du W">W Du</name></author><author><name sortKey="Dai, M" uniqKey="Dai M">M Dai</name></author><author><name sortKey="Li, Z" uniqKey="Li Z">Z Li</name></author><author><name sortKey="Boons, Gj" uniqKey="Boons G">GJ Boons</name></author><author><name sortKey="Peeters, B" uniqKey="Peeters B">B Peeters</name></author><author><name sortKey="Van Kuppeveld, Fjm" uniqKey="Van Kuppeveld F">FJM van Kuppeveld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kobasa, D" uniqKey="Kobasa D">D Kobasa</name></author><author><name sortKey="Kodihalli, S" uniqKey="Kodihalli S">S Kodihalli</name></author><author><name sortKey="Luo, M" uniqKey="Luo M">M Luo</name></author><author><name sortKey="Castrucci, Mr" uniqKey="Castrucci M">MR Castrucci</name></author><author><name sortKey="Donatelli, I" uniqKey="Donatelli I">I Donatelli</name></author><author><name sortKey="Suzuki, Y" uniqKey="Suzuki Y">Y Suzuki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uhlendorff, J" uniqKey="Uhlendorff J">J Uhlendorff</name></author><author><name sortKey="Matrosovich, T" uniqKey="Matrosovich T">T Matrosovich</name></author><author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name></author><author><name sortKey="Matrosovich, M" uniqKey="Matrosovich M">M Matrosovich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Varghese, Jn" uniqKey="Varghese J">JN Varghese</name></author><author><name sortKey="Colman, Pm" uniqKey="Colman P">PM Colman</name></author><author><name sortKey="Van Donkelaar, A" uniqKey="Van Donkelaar A">A van Donkelaar</name></author><author><name sortKey="Blick, Tj" uniqKey="Blick T">TJ Blick</name></author><author><name sortKey="Sahasrabudhe, A" uniqKey="Sahasrabudhe A">A Sahasrabudhe</name></author><author><name sortKey="Mckimm Breschkin, Jl" uniqKey="Mckimm Breschkin J">JL McKimm-Breschkin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sun, X" uniqKey="Sun X">X Sun</name></author><author><name sortKey="Li, Q" uniqKey="Li Q">Q Li</name></author><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y Wu</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Qi, J" uniqKey="Qi J">J Qi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai, Jc" uniqKey="Lai J">JC Lai</name></author><author><name sortKey="Garcia, Jm" uniqKey="Garcia J">JM Garcia</name></author><author><name sortKey="Dyason, Jc" uniqKey="Dyason J">JC Dyason</name></author><author><name sortKey="Bohm, R" uniqKey="Bohm R">R Bohm</name></author><author><name sortKey="Madge, Pd" uniqKey="Madge P">PD Madge</name></author><author><name sortKey="Rose, Fj" uniqKey="Rose F">FJ Rose</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nuss, Jm" uniqKey="Nuss J">JM Nuss</name></author><author><name sortKey="Air, Gm" uniqKey="Air G">GM Air</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dai, M" uniqKey="Dai M">M Dai</name></author><author><name sortKey="Mcbride, R" uniqKey="Mcbride R">R McBride</name></author><author><name sortKey="Dortmans, Jc" uniqKey="Dortmans J">JC Dortmans</name></author><author><name sortKey="Peng, W" uniqKey="Peng W">W Peng</name></author><author><name sortKey="Bakkers, Mj" uniqKey="Bakkers M">MJ Bakkers</name></author><author><name sortKey="De Groot, Rj" uniqKey="De Groot R">RJ de Groot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kobasa, D" uniqKey="Kobasa D">D Kobasa</name></author><author><name sortKey="Rodgers, Me" uniqKey="Rodgers M">ME Rodgers</name></author><author><name sortKey="Wells, K" uniqKey="Wells K">K Wells</name></author><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y Kawaoka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hausmann, J" uniqKey="Hausmann J">J Hausmann</name></author><author><name sortKey="Kretzschmar, E" uniqKey="Kretzschmar E">E Kretzschmar</name></author><author><name sortKey="Garten, W" uniqKey="Garten W">W Garten</name></author><author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matrosovich, Mn" uniqKey="Matrosovich M">MN Matrosovich</name></author><author><name sortKey="Krauss, S" uniqKey="Krauss S">S Krauss</name></author><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guo, H" uniqKey="Guo H">H Guo</name></author><author><name sortKey="Rabouw, H" uniqKey="Rabouw H">H Rabouw</name></author><author><name sortKey="Slomp, A" uniqKey="Slomp A">A Slomp</name></author><author><name sortKey="Dai, M" uniqKey="Dai M">M Dai</name></author><author><name sortKey="Van Der Vegt, F" uniqKey="Van Der Vegt F">F van der Vegt</name></author><author><name sortKey="Van Lent, Jwm" uniqKey="Van Lent J">JWM van Lent</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sauter, Nk" uniqKey="Sauter N">NK Sauter</name></author><author><name sortKey="Bednarski, Md" uniqKey="Bednarski M">MD Bednarski</name></author><author><name sortKey="Wurzburg, Ba" uniqKey="Wurzburg B">BA Wurzburg</name></author><author><name sortKey="Hanson, Je" uniqKey="Hanson J">JE Hanson</name></author><author><name sortKey="Whitesides, Gm" uniqKey="Whitesides G">GM Whitesides</name></author><author><name sortKey="Skehel, Jj" uniqKey="Skehel J">JJ Skehel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takemoto, Dk" uniqKey="Takemoto D">DK Takemoto</name></author><author><name sortKey="Skehel, Jj" uniqKey="Skehel J">JJ Skehel</name></author><author><name sortKey="Wiley, Dc" uniqKey="Wiley D">DC Wiley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, Am" uniqKey="Wu A">AM Wu</name></author><author><name sortKey="Wu, Jh" uniqKey="Wu J">JH Wu</name></author><author><name sortKey="Tsai, Ms" uniqKey="Tsai M">MS Tsai</name></author><author><name sortKey="Yang, Z" uniqKey="Yang Z">Z Yang</name></author><author><name sortKey="Sharon, N" uniqKey="Sharon N">N Sharon</name></author><author><name sortKey="Herp, A" uniqKey="Herp A">A Herp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sharma, V" uniqKey="Sharma V">V Sharma</name></author><author><name sortKey="Srinivas, Vr" uniqKey="Srinivas V">VR Srinivas</name></author><author><name sortKey="Adhikari, P" uniqKey="Adhikari P">P Adhikari</name></author><author><name sortKey="Vijayan, M" uniqKey="Vijayan M">M Vijayan</name></author><author><name sortKey="Surolia, A" uniqKey="Surolia A">A Surolia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Geisler, C" uniqKey="Geisler C">C Geisler</name></author><author><name sortKey="Jarvis, Dl" uniqKey="Jarvis D">DL Jarvis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shibuya, N" uniqKey="Shibuya N">N Shibuya</name></author><author><name sortKey="Goldstein, Ij" uniqKey="Goldstein I">IJ Goldstein</name></author><author><name sortKey="Broekaert, Wf" uniqKey="Broekaert W">WF Broekaert</name></author><author><name sortKey="Nsimba Lubaki, M" uniqKey="Nsimba Lubaki M">M Nsimba-Lubaki</name></author><author><name sortKey="Peeters, B" uniqKey="Peeters B">B Peeters</name></author><author><name sortKey="Peumans, Wj" uniqKey="Peumans W">WJ Peumans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baenziger, Ju" uniqKey="Baenziger J">JU Baenziger</name></author><author><name sortKey="Fiete, D" uniqKey="Fiete D">D Fiete</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spik, G" uniqKey="Spik G">G Spik</name></author><author><name sortKey="Bayard, B" uniqKey="Bayard B">B Bayard</name></author><author><name sortKey="Fournet, B" uniqKey="Fournet B">B Fournet</name></author><author><name sortKey="Strecker, G" uniqKey="Strecker G">G Strecker</name></author><author><name sortKey="Bouquelet, S" uniqKey="Bouquelet S">S Bouquelet</name></author><author><name sortKey="Montreuil, J" uniqKey="Montreuil J">J Montreuil</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Von Bonsdorff, L" uniqKey="Von Bonsdorff L">L von Bonsdorff</name></author><author><name sortKey="Tolo, H" uniqKey="Tolo H">H Tölö</name></author><author><name sortKey="Lindeberg, E" uniqKey="Lindeberg E">E Lindeberg</name></author><author><name sortKey="Nyman, T" uniqKey="Nyman T">T Nyman</name></author><author><name sortKey="Harju, A" uniqKey="Harju A">A Harju</name></author><author><name sortKey="Parkkinen, J" uniqKey="Parkkinen J">J Parkkinen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai, Jc" uniqKey="Lai J">JC Lai</name></author><author><name sortKey="Chan, Ww" uniqKey="Chan W">WW Chan</name></author><author><name sortKey="Kien, F" uniqKey="Kien F">F Kien</name></author><author><name sortKey="Nicholls, Jm" uniqKey="Nicholls J">JM Nicholls</name></author><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Garcia, Jm" uniqKey="Garcia J">JM Garcia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Del Piccolo, N" uniqKey="Del Piccolo N">N Del Piccolo</name></author><author><name sortKey="Placone, J" uniqKey="Placone J">J Placone</name></author><author><name sortKey="He, L" uniqKey="He L">L He</name></author><author><name sortKey="Agudelo, Sc" uniqKey="Agudelo S">SC Agudelo</name></author><author><name sortKey="Hristova, K" uniqKey="Hristova K">K Hristova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hatakeyama, S" uniqKey="Hatakeyama S">S Hatakeyama</name></author><author><name sortKey="Sakai Tagawa, Y" uniqKey="Sakai Tagawa Y">Y Sakai-Tagawa</name></author><author><name sortKey="Kiso, M" uniqKey="Kiso M">M Kiso</name></author><author><name sortKey="Goto, H" uniqKey="Goto H">H Goto</name></author><author><name sortKey="Kawakami, C" uniqKey="Kawakami C">C Kawakami</name></author><author><name sortKey="Mitamura, K" uniqKey="Mitamura K">K Mitamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Govorkova, Ea" uniqKey="Govorkova E">EA Govorkova</name></author><author><name sortKey="Murti, G" uniqKey="Murti G">G Murti</name></author><author><name sortKey="Meignier, B" uniqKey="Meignier B">B Meignier</name></author><author><name sortKey="De Taisne, C" uniqKey="De Taisne C">C de Taisne</name></author><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Carlsson, Sr" uniqKey="Carlsson S">SR Carlsson</name></author><author><name sortKey="Lycksell, Po" uniqKey="Lycksell P">PO Lycksell</name></author><author><name sortKey="Fukuda, M" uniqKey="Fukuda M">M Fukuda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carlsson, Sr" uniqKey="Carlsson S">SR Carlsson</name></author><author><name sortKey="Roth, J" uniqKey="Roth J">J Roth</name></author><author><name sortKey="Piller, F" uniqKey="Piller F">F Piller</name></author><author><name sortKey="Fukuda, M" uniqKey="Fukuda M">M Fukuda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoshima, H" uniqKey="Yoshima H">H Yoshima</name></author><author><name sortKey="Furthmayr, H" uniqKey="Furthmayr H">H Furthmayr</name></author><author><name sortKey="Kobata, A" uniqKey="Kobata A">A Kobata</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zdebska, E" uniqKey="Zdebska E">E Zdebska</name></author><author><name sortKey="Koscielak, J" uniqKey="Koscielak J">J Koscielak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Poucke, S" uniqKey="Van Poucke S">S Van Poucke</name></author><author><name sortKey="Doedt, J" uniqKey="Doedt J">J Doedt</name></author><author><name sortKey="Baumann, J" uniqKey="Baumann J">J Baumann</name></author><author><name sortKey="Qiu, Y" uniqKey="Qiu Y">Y Qiu</name></author><author><name sortKey="Matrosovich, T" uniqKey="Matrosovich T">T Matrosovich</name></author><author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matrosovich, M" uniqKey="Matrosovich M">M Matrosovich</name></author><author><name sortKey="Matrosovich, T" uniqKey="Matrosovich T">T Matrosovich</name></author><author><name sortKey="Uhlendorff, J" uniqKey="Uhlendorff J">J Uhlendorff</name></author><author><name sortKey="Garten, W" uniqKey="Garten W">W Garten</name></author><author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Laver, Wg" uniqKey="Laver W">WG Laver</name></author><author><name sortKey="Colman, Pm" uniqKey="Colman P">PM Colman</name></author><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author><author><name sortKey="Hinshaw, Vs" uniqKey="Hinshaw V">VS Hinshaw</name></author><author><name sortKey="Air, Gm" uniqKey="Air G">GM Air</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Benton, Dj" uniqKey="Benton D">DJ Benton</name></author><author><name sortKey="Wharton, Sa" uniqKey="Wharton S">SA Wharton</name></author><author><name sortKey="Martin, Sr" uniqKey="Martin S">SR Martin</name></author><author><name sortKey="Mccauley, Jw" uniqKey="Mccauley J">JW McCauley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, Yp" uniqKey="Lin Y">YP Lin</name></author><author><name sortKey="Gregory, V" uniqKey="Gregory V">V Gregory</name></author><author><name sortKey="Collins, P" uniqKey="Collins P">P Collins</name></author><author><name sortKey="Kloess, J" uniqKey="Kloess J">J Kloess</name></author><author><name sortKey="Wharton, S" uniqKey="Wharton S">S Wharton</name></author><author><name sortKey="Cattle, N" uniqKey="Cattle N">N Cattle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mogling, R" uniqKey="Mogling R">R Mogling</name></author><author><name sortKey="Richard, Mj" uniqKey="Richard M">MJ Richard</name></author><author><name sortKey="Vliet, Sv" uniqKey="Vliet S">SV Vliet</name></author><author><name sortKey="Beek, Rv" uniqKey="Beek R">RV Beek</name></author><author><name sortKey="Schrauwen, Eja" uniqKey="Schrauwen E">EJA Schrauwen</name></author><author><name sortKey="Spronken, Mi" uniqKey="Spronken M">MI Spronken</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai, Jcc" uniqKey="Lai J">JCC Lai</name></author><author><name sortKey="Karunarathna, H" uniqKey="Karunarathna H">H Karunarathna</name></author><author><name sortKey="Wong, Hh" uniqKey="Wong H">HH Wong</name></author><author><name sortKey="Peiris, Jsm" uniqKey="Peiris J">JSM Peiris</name></author><author><name sortKey="Nicholls, Jm" uniqKey="Nicholls J">JM Nicholls</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author><author><name sortKey="Air, Gm" uniqKey="Air G">GM Air</name></author><author><name sortKey="Metzger, Dw" uniqKey="Metzger D">DW Metzger</name></author><author><name sortKey="Colman, Pm" uniqKey="Colman P">PM Colman</name></author><author><name sortKey="Varghese, Jn" uniqKey="Varghese J">JN Varghese</name></author><author><name sortKey="Baker, At" uniqKey="Baker A">AT Baker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bakkers, Mj" uniqKey="Bakkers M">MJ Bakkers</name></author><author><name sortKey="Lang, Y" uniqKey="Lang Y">Y Lang</name></author><author><name sortKey="Feitsma, Lj" uniqKey="Feitsma L">LJ Feitsma</name></author><author><name sortKey="Hulswit, Rj" uniqKey="Hulswit R">RJ Hulswit</name></author><author><name sortKey="De Poot, Sa" uniqKey="De Poot S">SA de Poot</name></author><author><name sortKey="Van Vliet, Al" uniqKey="Van Vliet A">AL van Vliet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cornelissen, La" uniqKey="Cornelissen L">LA Cornelissen</name></author><author><name sortKey="De Vries, Rp" uniqKey="De Vries R">RP de Vries</name></author><author><name sortKey="De Boer Luijtze, Ea" uniqKey="De Boer Luijtze E">EA de Boer-Luijtze</name></author><author><name sortKey="Rigter, A" uniqKey="Rigter A">A Rigter</name></author><author><name sortKey="Rottier, Pj" uniqKey="Rottier P">PJ Rottier</name></author><author><name sortKey="De Haan, Ca" uniqKey="De Haan C">CA de Haan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Predonzani, A" uniqKey="Predonzani A">A Predonzani</name></author><author><name sortKey="Arnoldi, F" uniqKey="Arnoldi F">F Arnoldi</name></author><author><name sortKey="Lopez Requena, A" uniqKey="Lopez Requena A">A Lopez-Requena</name></author><author><name sortKey="Burrone, Or" uniqKey="Burrone O">OR Burrone</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="James, Kt" uniqKey="James K">KT James</name></author><author><name sortKey="Cooney, B" uniqKey="Cooney B">B Cooney</name></author><author><name sortKey="Agopsowicz, K" uniqKey="Agopsowicz K">K Agopsowicz</name></author><author><name sortKey="Trevors, Ma" uniqKey="Trevors M">MA Trevors</name></author><author><name sortKey="Mohamed, A" uniqKey="Mohamed A">A Mohamed</name></author><author><name sortKey="Stoltz, D" uniqKey="Stoltz D">D Stoltz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Potier, M" uniqKey="Potier M">M Potier</name></author><author><name sortKey="Mameli, L" uniqKey="Mameli L">L Mameli</name></author><author><name sortKey="Belisle, M" uniqKey="Belisle M">M Bélisle</name></author><author><name sortKey="Dallaire, L" uniqKey="Dallaire L">L Dallaire</name></author><author><name sortKey="Melancon, Sb" uniqKey="Melancon S">SB Melançon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matrosovich, M" uniqKey="Matrosovich M">M Matrosovich</name></author><author><name sortKey="Matrosovich, T" uniqKey="Matrosovich T">T Matrosovich</name></author><author><name sortKey="Garten, W" uniqKey="Garten W">W Garten</name></author><author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vavricka, Cj" uniqKey="Vavricka C">CJ Vavricka</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Kiyota, H" uniqKey="Kiyota H">H Kiyota</name></author><author><name sortKey="Sriwilaijaroen, N" uniqKey="Sriwilaijaroen N">N Sriwilaijaroen</name></author><author><name sortKey="Qi, J" uniqKey="Qi J">J Qi</name></author><author><name sortKey="Tanaka, K" uniqKey="Tanaka K">K Tanaka</name></author><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y Wu</name></author><author><name sortKey="Li, Q" uniqKey="Li Q">Q Li</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Yan, J" uniqKey="Yan J">J Yan</name></author><author><name sortKey="Suzuki, Y" uniqKey="Suzuki Y">Y Suzuki</name></author><author><name sortKey="Gao, Gf" uniqKey="Gao G">GF Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, J" uniqKey="Xu J">J Xu</name></author><author><name sortKey="Davis, Ct" uniqKey="Davis C">CT Davis</name></author><author><name sortKey="Christman, Mc" uniqKey="Christman M">MC Christman</name></author><author><name sortKey="Rivailler, P" uniqKey="Rivailler P">P Rivailler</name></author><author><name sortKey="Zhong, H" uniqKey="Zhong H">H Zhong</name></author><author><name sortKey="Donis, Ro" uniqKey="Donis R">RO Donis</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Pays-Bas</li></country><region><li>District de Giessen</li><li>Hesse (Land)</li><li>Utrecht (province)</li></region><settlement><li>Marbourg</li><li>Utrecht</li></settlement><orgName><li>Université d'Utrecht</li></orgName></list><tree><country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Du, Wenjuan" sort="Du, Wenjuan" uniqKey="Du W" first="Wenjuan" last="Du">Wenjuan Du</name></region><name sortKey="Boons, Geert Jan" sort="Boons, Geert Jan" uniqKey="Boons G" first="Geert-Jan" last="Boons">Geert-Jan Boons</name><name sortKey="De Haan, Cornelis A M" sort="De Haan, Cornelis A M" uniqKey="De Haan C" first="Cornelis A. M." last="De Haan">Cornelis A. M. De Haan</name><name sortKey="De Vries, Erik" sort="De Vries, Erik" uniqKey="De Vries E" first="Erik" last="De Vries">Erik De Vries</name><name sortKey="Guo, Hongbo" sort="Guo, Hongbo" uniqKey="Guo H" first="Hongbo" last="Guo">Hongbo Guo</name><name sortKey="Li, Zeshi" sort="Li, Zeshi" uniqKey="Li Z" first="Zeshi" last="Li">Zeshi Li</name><name sortKey="Nijman, Vera S" sort="Nijman, Vera S" uniqKey="Nijman V" first="Vera S." last="Nijman">Vera S. Nijman</name><name sortKey="Van Der Lee, Joline" sort="Van Der Lee, Joline" uniqKey="Van Der Lee J" first="Joline" last="Van Der Lee">Joline Van Der Lee</name><name sortKey="Van Der Vries, Erhard" sort="Van Der Vries, Erhard" uniqKey="Van Der Vries E" first="Erhard" last="Van Der Vries">Erhard Van Der Vries</name><name sortKey="Van Kuppeveld, Frank J M" sort="Van Kuppeveld, Frank J M" uniqKey="Van Kuppeveld F" first="Frank J. M." last="Van Kuppeveld">Frank J. M. Van Kuppeveld</name></country><country name="Allemagne"><region name="Hesse (Land)"><name sortKey="Doedt, Jennifer" sort="Doedt, Jennifer" uniqKey="Doedt J" first="Jennifer" last="Doedt">Jennifer Doedt</name></region><name sortKey="Matrosovich, Mikhail" sort="Matrosovich, Mikhail" uniqKey="Matrosovich M" first="Mikhail" last="Matrosovich">Mikhail Matrosovich</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/H2N2V1/Data/1957/Analysis
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000005 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/1957/Analysis/biblio.hfd -nk 000005 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= H2N2V1
|flux= 1957
|étape= Analysis
|type= RBID
|clé= PMC:6586374
|texte= The 2nd sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/1957/Analysis/RBID.i -Sk "pubmed:31181126" \
| HfdSelect -Kh $EXPLOR_AREA/Data/1957/Analysis/biblio.hfd \
| NlmPubMed2Wicri -a H2N2V1
| This area was generated with Dilib version V0.6.33. |  |