Evolution of the receptor binding properties of the influenza A(H3N2) hemagglutinin
The hemagglutinin (HA) of influenza A(H3N2) virus responsible for the 1968 influenza pandemic derived from an avian virus. On introduction into humans, its receptor binding properties had changed from a preference for avian receptors (α2,3-linked sialic acid) to a preference for human receptors (α2,6-linked sialic acid). By 2001, the avidity of human H3 viruses for avian receptors had declined, and since then the affinity for human receptors has also decreased significantly. These changes in receptor binding, which correlate with increased difficulties in virus propagation in vitro and in antigenic analysis, have been assessed by virus hemagglutination of erythrocytes from different species and quantified by measuring virus binding to receptor analogs using surface biolayer interferometry. Crystal structures of HA-receptor analog complexes formed with HAs from viruses isolated in 2004 and 2005 reveal significant differences in the conformation of the 220-loop of HA1, relative to the 1968 structure, resulting in altered interactions between the HA and the receptor analog that explain the changes in receptor affinity. Site-specific mutagenesis shows the HA1 Asp-225→Asn substitution to be the key determinant of the decreased receptor binding in viruses circulating since 2005. Our results indicate that the evolution of human influenza A(H3N2) viruses since 1968 has produced a virus with a low propensity to bind human receptor analogs, and this loss of avidity correlates with the marked reduction in A(H3N2) virus disease impact in the last 10 y.
| Errataetall: |
ErratumIn: Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2677 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:109 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 109(2012), 52 vom: 26. Dez., Seite 21474-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lin, Yi Pu [VerfasserIn] |
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| Links: |
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| Themen: |
GZP2782OP0 |
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| Anmerkungen: |
Date Completed 21.02.2013 Date Revised 29.01.2022 published: Print-Electronic PDB: 2YP2, 2YP3, 2YP4, 2YP5, 2YP7, 2YP8, 2YP9, 2YPG ErratumIn: Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2677 Citation Status MEDLINE |
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| doi: |
10.1073/pnas.1218841110 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM223406643 |
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| 245 | 1 | 0 | |a Evolution of the receptor binding properties of the influenza A(H3N2) hemagglutinin |
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| 500 | |a ErratumIn: Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2677 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The hemagglutinin (HA) of influenza A(H3N2) virus responsible for the 1968 influenza pandemic derived from an avian virus. On introduction into humans, its receptor binding properties had changed from a preference for avian receptors (α2,3-linked sialic acid) to a preference for human receptors (α2,6-linked sialic acid). By 2001, the avidity of human H3 viruses for avian receptors had declined, and since then the affinity for human receptors has also decreased significantly. These changes in receptor binding, which correlate with increased difficulties in virus propagation in vitro and in antigenic analysis, have been assessed by virus hemagglutination of erythrocytes from different species and quantified by measuring virus binding to receptor analogs using surface biolayer interferometry. Crystal structures of HA-receptor analog complexes formed with HAs from viruses isolated in 2004 and 2005 reveal significant differences in the conformation of the 220-loop of HA1, relative to the 1968 structure, resulting in altered interactions between the HA and the receptor analog that explain the changes in receptor affinity. Site-specific mutagenesis shows the HA1 Asp-225→Asn substitution to be the key determinant of the decreased receptor binding in viruses circulating since 2005. Our results indicate that the evolution of human influenza A(H3N2) viruses since 1968 has produced a virus with a low propensity to bind human receptor analogs, and this loss of avidity correlates with the marked reduction in A(H3N2) virus disease impact in the last 10 y | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Hemagglutinin Glycoproteins, Influenza Virus |2 NLM | |
| 650 | 7 | |a Receptors, Virus |2 NLM | |
| 650 | 7 | |a N-Acetylneuraminic Acid |2 NLM | |
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| 700 | 1 | |a Xiong, Xiaoli |e verfasserin |4 aut | |
| 700 | 1 | |a Wharton, Stephen A |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Stephen R |e verfasserin |4 aut | |
| 700 | 1 | |a Coombs, Peter J |e verfasserin |4 aut | |
| 700 | 1 | |a Vachieri, Sebastien G |e verfasserin |4 aut | |
| 700 | 1 | |a Christodoulou, Evangelos |e verfasserin |4 aut | |
| 700 | 1 | |a Walker, Philip A |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Junfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Skehel, John J |e verfasserin |4 aut | |
| 700 | 1 | |a Gamblin, Steven J |e verfasserin |4 aut | |
| 700 | 1 | |a Hay, Alan J |e verfasserin |4 aut | |
| 700 | 1 | |a Daniels, Rodney S |e verfasserin |4 aut | |
| 700 | 1 | |a McCauley, John W |e verfasserin |4 aut | |
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