Receptor binding by a ferret-transmissible H5 avian influenza virus
Cell-surface-receptor binding by influenza viruses is a key determinant of their transmissibility, both from avian and animal species to humans as well as from human to human. Highly pathogenic avian H5N1 viruses that are a threat to public health have been observed to acquire affinity for human receptors, and transmissible-mutant-selection experiments have identified a virus that is transmissible in ferrets, the generally accepted experimental model for influenza in humans. Here, our quantitative biophysical measurements of the receptor-binding properties of haemagglutinin (HA) from the transmissible mutant indicate a small increase in affinity for human receptor and a marked decrease in affinity for avian receptor. From analysis of virus and HA binding data we have derived an algorithm that predicts virus avidity from the affinity of individual HA-receptor interactions. It reveals that the transmissible-mutant virus has a 200-fold preference for binding human over avian receptors. The crystal structure of the transmissible-mutant HA in complex with receptor analogues shows that it has acquired the ability to bind human receptor in the same folded-back conformation as seen for HA from the 1918, 1957 (ref. 4), 1968 (ref. 5) and 2009 (ref. 6) pandemic viruses. This binding mode is substantially different from that by which non-transmissible wild-type H5 virus HA binds human receptor. The structure of the complex also explains how the change in preference from avian to human receptors arises from the Gln226Leu substitution, which facilitates binding to human receptor but restricts binding to avian receptor. Both features probably contribute to the acquisition of transmissibility by this mutant virus.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2013 |
|---|---|
| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:497 |
|---|---|
| Enthalten in: |
Nature - 497(2013), 7449 vom: 16. Mai, Seite 392-6 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Xiong, Xiaoli [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Hemagglutinin Glycoproteins, Influenza Virus |
|---|
| Anmerkungen: |
Date Completed 04.06.2013 Date Revised 21.10.2021 published: Print-Electronic PDB: 4BGW, 4BGX, 4BGY, 4BGZ, 4BH0, 4BH1, 4BH2, 4BH3, 4BH4 Citation Status MEDLINE |
|---|
| doi: |
10.1038/nature12144 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM22696065X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM22696065X | ||
| 003 | DE-627 | ||
| 005 | 20231224072608.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2013 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/nature12144 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0756.xml |
| 035 | |a (DE-627)NLM22696065X | ||
| 035 | |a (NLM)23615615 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Xiong, Xiaoli |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Receptor binding by a ferret-transmissible H5 avian influenza virus |
| 264 | 1 | |c 2013 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.06.2013 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a PDB: 4BGW, 4BGX, 4BGY, 4BGZ, 4BH0, 4BH1, 4BH2, 4BH3, 4BH4 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Cell-surface-receptor binding by influenza viruses is a key determinant of their transmissibility, both from avian and animal species to humans as well as from human to human. Highly pathogenic avian H5N1 viruses that are a threat to public health have been observed to acquire affinity for human receptors, and transmissible-mutant-selection experiments have identified a virus that is transmissible in ferrets, the generally accepted experimental model for influenza in humans. Here, our quantitative biophysical measurements of the receptor-binding properties of haemagglutinin (HA) from the transmissible mutant indicate a small increase in affinity for human receptor and a marked decrease in affinity for avian receptor. From analysis of virus and HA binding data we have derived an algorithm that predicts virus avidity from the affinity of individual HA-receptor interactions. It reveals that the transmissible-mutant virus has a 200-fold preference for binding human over avian receptors. The crystal structure of the transmissible-mutant HA in complex with receptor analogues shows that it has acquired the ability to bind human receptor in the same folded-back conformation as seen for HA from the 1918, 1957 (ref. 4), 1968 (ref. 5) and 2009 (ref. 6) pandemic viruses. This binding mode is substantially different from that by which non-transmissible wild-type H5 virus HA binds human receptor. The structure of the complex also explains how the change in preference from avian to human receptors arises from the Gln226Leu substitution, which facilitates binding to human receptor but restricts binding to avian receptor. Both features probably contribute to the acquisition of transmissibility by this mutant virus | ||
| 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 | |
| 700 | 1 | |a Coombs, Peter J |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Stephen R |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Junfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Haixia |e verfasserin |4 aut | |
| 700 | 1 | |a McCauley, John W |e verfasserin |4 aut | |
| 700 | 1 | |a Locher, Kathrin |e verfasserin |4 aut | |
| 700 | 1 | |a Walker, Philip A |e verfasserin |4 aut | |
| 700 | 1 | |a Collins, Patrick J |e verfasserin |4 aut | |
| 700 | 1 | |a Kawaoka, Yoshihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Skehel, John J |e verfasserin |4 aut | |
| 700 | 1 | |a Gamblin, Steven J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature |d 1945 |g 497(2013), 7449 vom: 16. Mai, Seite 392-6 |w (DE-627)NLM000008257 |x 1476-4687 |7 nnns |
| 773 | 1 | 8 | |g volume:497 |g year:2013 |g number:7449 |g day:16 |g month:05 |g pages:392-6 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/nature12144 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 497 |j 2013 |e 7449 |b 16 |c 05 |h 392-6 | ||