File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Structural basis and sequence co-evolution analysis of the hemagglutinin protein of pandemic influenza A/H1N1 (2009) virus

TitleStructural basis and sequence co-evolution analysis of the hemagglutinin protein of pandemic influenza A/H1N1 (2009) virus
Authors
KeywordsCo-evolution
D222g
Hemagglutinin
Influenza a
Pandemic
Structural evolution
Issue Date2011
PublisherSociety for Experimental Biology and Medicine. The Journal's web site is located at http://www.ebmonline.org/
Citation
Experimental Biology And Medicine, 2011, v. 236 n. 8, p. 915-925 How to Cite?
AbstractSevere pandemic influenza A H1N1 (2009) infection, especially in the lower respiratory tract, is often associated with the virus carrying a D222G substitution in the hemagglutinin (HA) protein of the virus. The mechanism for this association has not been fully explored. In the in vitro binding assay, it was found that clinical isolates carrying D222G substitution exhibit higher binding avidity to 2,3-linked sialic acids than the wild-type virus. The receptor binding pocket of the pandemic influenza (H1N1) HA was found to be smaller than those of other influenza A strains, allowing tighter binding of the virus with the receptor, yet also inducing steric stress for the binding. Our homology modeling and molecular docking calculations implicated that residue 222 may affect the positioning of the conserved Q223 residue, hence modulating flexibility of the binding pocket and steric hindrance during receptor binding. The molecular property of residue 222 can also directly influence the 'lysine fence' via the polarity of the amino acid residue where D222G substitution will enhance the electrostatic interactions between the receptor and the protein. The potential importance of residue 222 was illustrated by evolutionary analysis, which showed that this site is under intense selection pressure during adaptation of the virus to human host. Our findings provide a useful reference for follow-up studies in monitoring the ongoing evolution of the pandemic influenza A H1N1 (2009) virus. © 2011 by the Society for Experimental Biology and Medicine.
Persistent Identifierhttp://hdl.handle.net/10722/142329
ISSN
2014 Impact Factor: 2.165
2014 SCImago Journal Rankings: 0.832
ISI Accession Number ID
Funding AgencyGrant Number
Ted Sun Foundation
Providence Foundation Limited
Hong Kong Special Administrative Region Research Grant Council
Food and Health Bureau of the Hong Kong Special Administrative Region
Shaw Foundation
Funding Information:

This work is partly supported by the Ted Sun Foundation, Providence Foundation Limited in memory of the late Dr Lui Hac Minh, the Hong Kong Special Administrative Region Research Grant Council, Research Fund for the Control of Infectious Diseases of the Food and Health Bureau of the Hong Kong Special Administrative Region, and The Shaw Foundation. We thank Dr Kelvin To for reading the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorTse, Hen_HK
dc.contributor.authorKao, RYTen_HK
dc.contributor.authorWu, WLen_HK
dc.contributor.authorLim, WWLen_HK
dc.contributor.authorChen, Hen_HK
dc.contributor.authorYeung, MYen_HK
dc.contributor.authorWoo, PCYen_HK
dc.contributor.authorSze, KHen_HK
dc.contributor.authorYuen, KYen_HK
dc.date.accessioned2011-10-28T02:43:13Z-
dc.date.available2011-10-28T02:43:13Z-
dc.date.issued2011en_HK
dc.identifier.citationExperimental Biology And Medicine, 2011, v. 236 n. 8, p. 915-925en_HK
dc.identifier.issn1535-3702en_HK
dc.identifier.urihttp://hdl.handle.net/10722/142329-
dc.description.abstractSevere pandemic influenza A H1N1 (2009) infection, especially in the lower respiratory tract, is often associated with the virus carrying a D222G substitution in the hemagglutinin (HA) protein of the virus. The mechanism for this association has not been fully explored. In the in vitro binding assay, it was found that clinical isolates carrying D222G substitution exhibit higher binding avidity to 2,3-linked sialic acids than the wild-type virus. The receptor binding pocket of the pandemic influenza (H1N1) HA was found to be smaller than those of other influenza A strains, allowing tighter binding of the virus with the receptor, yet also inducing steric stress for the binding. Our homology modeling and molecular docking calculations implicated that residue 222 may affect the positioning of the conserved Q223 residue, hence modulating flexibility of the binding pocket and steric hindrance during receptor binding. The molecular property of residue 222 can also directly influence the 'lysine fence' via the polarity of the amino acid residue where D222G substitution will enhance the electrostatic interactions between the receptor and the protein. The potential importance of residue 222 was illustrated by evolutionary analysis, which showed that this site is under intense selection pressure during adaptation of the virus to human host. Our findings provide a useful reference for follow-up studies in monitoring the ongoing evolution of the pandemic influenza A H1N1 (2009) virus. © 2011 by the Society for Experimental Biology and Medicine.en_HK
dc.languageengen_US
dc.publisherSociety for Experimental Biology and Medicine. The Journal's web site is located at http://www.ebmonline.org/en_HK
dc.relation.ispartofExperimental Biology and Medicineen_HK
dc.subjectCo-evolutionen_HK
dc.subjectD222gen_HK
dc.subjectHemagglutininen_HK
dc.subjectInfluenza aen_HK
dc.subjectPandemicen_HK
dc.subjectStructural evolutionen_HK
dc.subject.meshBinding Sites-
dc.subject.meshDisease Outbreaks-
dc.subject.meshEvolution, Molecular-
dc.subject.meshHemagglutinin Glycoproteins, Influenza Virus - chemistry - genetics-
dc.subject.meshInfluenza A Virus, H1N1 Subtype - genetics - immunology-
dc.titleStructural basis and sequence co-evolution analysis of the hemagglutinin protein of pandemic influenza A/H1N1 (2009) virusen_HK
dc.typeArticleen_HK
dc.identifier.emailTse, H:herman@graduate.hku.hken_HK
dc.identifier.emailKao, RYT:rytkao@hkucc.hku.hken_HK
dc.identifier.emailChen, H:hlchen@hkucc.hku.hken_HK
dc.identifier.emailWoo, PCY:pcywoo@hkucc.hku.hken_HK
dc.identifier.emailSze, KH:khsze@hku.hken_HK
dc.identifier.emailYuen, KY:kyyuen@hkucc.hku.hken_HK
dc.identifier.authorityTse, H=rp00519en_HK
dc.identifier.authorityKao, RYT=rp00481en_HK
dc.identifier.authorityChen, H=rp00383en_HK
dc.identifier.authorityWoo, PCY=rp00430en_HK
dc.identifier.authoritySze, KH=rp00785en_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1258/ebm.2011.010264en_HK
dc.identifier.pmid21727184-
dc.identifier.scopuseid_2-s2.0-79961186167en_HK
dc.identifier.hkuros197184en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79961186167&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume236en_HK
dc.identifier.issue8en_HK
dc.identifier.spage915en_HK
dc.identifier.epage925en_HK
dc.identifier.eissn1535-3699-
dc.identifier.isiWOS:000293877200004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTse, H=7006070596en_HK
dc.identifier.scopusauthoridKao, RYT=7101675499en_HK
dc.identifier.scopusauthoridWu, WL=54394651900en_HK
dc.identifier.scopusauthoridLim, WWL=54393593900en_HK
dc.identifier.scopusauthoridChen, H=26643315400en_HK
dc.identifier.scopusauthoridYeung, MY=16029841800en_HK
dc.identifier.scopusauthoridWoo, PCY=7201801340en_HK
dc.identifier.scopusauthoridSze, KH=7006735061en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats