Structural basis for receptor specificity of influenza B virus hemagglutinin

doi:10.1073/pnas.0708363104

Structural basis for receptor specificity of influenza B virus hemagglutinin

*Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, BCM-125, Houston, TX 77030;
^‡Graduate Program in Structural Computational Biology and Molecular Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030; and
^§Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005

Communicated by William N. Lipscomb, Harvard University, Cambridge, MA, September 4, 2007 (received for review July 3, 2007)

Abstract

Receptor-binding specificity of HA, the major surface glycoprotein of influenza virus, primarily determines the host ranges that the virus can infect. Influenza type B virus almost exclusively infects humans and contributes to the annual “flu” sickness. Here we report the structures of influenza B virus HA in complex with human and avian receptor analogs, respectively. These structures provide a structural basis for the different receptor-binding properties of influenza A and B virus HA molecules and for the ability of influenza B virus HA to distinguish human and avian receptors. The structure of influenza B virus HA with avian receptor analog also reveals how mutations in the region of residues 194 to 196, which are frequently observed in egg-adapted and naturally occurring variants, directly affect the receptor binding of the resultant virus strains. Furthermore, these structures of influenza B virus HA are compared with known structures of influenza A virus HAs, which suggests the role of the residue at 222 as a key and likely a universal determinant for the different binding modes of human receptor analogs by different HA molecules.

Footnotes

^†To whom correspondence should be addressed. E-mail: qinghuaw{at}bcm.tmc.edu
Author contributions: Q.W. designed research; Q.W., X.T., and X.C. performed research; Q.W. and J.M. analyzed data; and Q.W. wrote the paper.
The authors declare no conflict of interest.
Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 2RFT and 2RFU).