Research abstract

Letter abstract

Nature Biotechnology 26, 107 - 113 (2008)
Published online: 6 January 2008 | doi:10.1038/nbt1375

Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin

Aarthi Chandrasekaran1,5, Aravind Srinivasan1,5, Rahul Raman1,5, Karthik Viswanathan1,5, S Raguram1, Terrence M Tumpey2, V Sasisekharan3 & Ram Sasisekharan1,3,4


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 humans1, 2, 3, 4. 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 population5, 6. Our findings will enable the development of additional strategies for effective surveillance and potential therapeutic interventions for H5N1 and possibly other influenza A viruses.

  1. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
  2. Influenza Division, Mailstop G-16, National Center for Immunization and Respiratory Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, NE, Atlanta, Georgia 30333, USA.
  3. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
  4. Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
  5. These authors contributed equally to this work.

Correspondence to: Ram Sasisekharan1,3,4 e-mail:


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