Document Detail


Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin.
MedLine Citation:
PMID:  18176555     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A switch in specificity of avian influenza A viruses' hemagglutinin (HA) from avian-like (alpha2-3 sialylated glycans) to human-like (alpha2-6 sialylated glycans) receptors is believed to be associated with their adaptation to infect humans. We show that a characteristic structural topology--and not the alpha2-6 linkage itself--enables specific binding of HA to alpha2-6 sialylated glycans and that recognition of this topology may be critical for adaptation of HA to bind glycans in the upper respiratory tract of humans. An integrated biochemical, analytical and data mining approach demonstrates that HAs from the human-adapted H1N1 and H3N2 viruses, but not H5N1 (bird flu) viruses, specifically bind to long alpha2-6 sialylated glycans with this topology. This could explain why H5N1 viruses have not yet gained a foothold in the human population. Our findings will enable the development of additional strategies for effective surveillance and potential therapeutic interventions for H5N1 and possibly other influenza A viruses.
Authors:
Aarthi Chandrasekaran; Aravind Srinivasan; Rahul Raman; Karthik Viswanathan; S Raguram; Terrence M Tumpey; V Sasisekharan; Ram Sasisekharan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-01-06
Journal Detail:
Title:  Nature biotechnology     Volume:  26     ISSN:  1546-1696     ISO Abbreviation:  Nat. Biotechnol.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-09     Completed Date:  2008-02-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9604648     Medline TA:  Nat Biotechnol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  107-13     Citation Subset:  IM    
Affiliation:
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological / genetics
Animals
Birds
Evolution, Molecular
Hemagglutinin Glycoproteins, Influenza Virus / genetics*
Humans
Influenza A Virus, H5N1 Subtype / genetics,  pathogenicity*,  physiology
Influenza in Birds / genetics*,  virology*
Influenza, Human / genetics*,  virology*
Mutation
Polysaccharides / genetics*
Grant Support
ID/Acronym/Agency:
GM57073/GM/NIGMS NIH HHS; U54 GM62116/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Hemagglutinin Glycoproteins, Influenza Virus; 0/Polysaccharides; 0/hemagglutinin, human influenza A virus

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