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Amino acid residues at positions 222 and 227 of the hemagglutinin together with the neuraminidase determine binding of H5 avian influenza viruses to sialyl Lewis X

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Abstract

Influenza viruses isolated from ducks are rarely able to infect chickens; it is therefore postulated that these viruses need to adapt in some way to be able to be transmitted to chickens in nature. Previous studies revealed that sialyl Lewis X (3′SLeX), which is fucosylated α2,3 sialoside, was predominantly detected on the epithelial cells of the chicken trachea, whereas this glycan structure is not found in the duck intestinal tract. To clarify the mechanisms of the interspecies transmission of influenza viruses between ducks and chickens, we compared the receptor specificity of low-pathogenic avian influenza viruses isolated from these two species. Glycan-binding analysis of the recombinant hemagglutinin (HA) of a chicken influenza virus, A/chicken/Ibaraki/1/2005 (H5N2), revealed a binding preference to α1,3 fucosylated sialosides. On the other hand, the HA of a duck influenza virus, A/duck/Mongolia/54/2001 (H5N2) (Dk/MNG), particularly bound to non-fucosylated α2,3 sialosides such as 3′-sialyllactosamine (3′SLacNAc). Computational analysis along with binding analysis of the mutant HAs revealed that this glycan-binding specificity of the HA was determined by amino acid residues at positions 222 and 227. Inconsistent with the glycan-binding specificity of the recombinant HA protein, virions of Dk/MNG bound to both 3′SLacNAc and 3′SLeX. Glycan-binding analysis in the presence of a neuraminidase (NA) inhibitor revealed that the NA conferred binding to 3′SLeX to virions of Dk/MNG. The present results reveal the molecular basis of the interaction between fucosylated α2,3 sialosides and influenza viruses.

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Acknowledgments

We thank Ms. Yuki Maki and Ms. Ana L. Tran-Crie for their kind help in organizing this collaborative effort. We thank Drs. Masanori Kobayashi and Keiichi Taniguchi of Shionogi & Co. Ltd., for providing peramivir and their technical advice. The present work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI (grant number 26850178 to M.O.) and by the Program for Leading Graduate Schools from JSPS (grant number F01). This work was funded in part by the National Institutes of Health Grant R56 (grant number AI099274 to J.C.P). Several glycans used for the HA binding assays were provided by the Consortium for Functional Glycomics (http://www.functionalglycomics.org/) funded by National Institute of General Medical Sciences (NIGMS) (grant number GM62116 to J.C.P.). R.P.d.V. is a recipient of Rubicon and VENI grants from the Netherlands Organization for Scientific Research (NWO). T.H. is supported by JSPS Research Fellowships for young scientists.

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Author notes

  1. Hiroshi Kida

    Present address: Research Center for Zoonosis Control, Hokkaido University, Kita 20 Nishi 10, Kita-ku, Sapporo, Hokkaido, 001-0020, Japan

  2. Robert P. de Vries

    Present address: Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG, Utrecht, The Netherlands

Authors and Affiliations

  1. Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan

    Takahiro Hiono, Masatoshi Okamatsu, Yoshihiro Sakoda & Hiroshi Kida

  2. Research Center for Zoonosis Control, Hokkaido University, Kita 20 Nishi 10, Kita-ku, Sapporo, Hokkaido, 001-0020, Japan

    Manabu Igarashi

  3. Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan

    Manabu Igarashi, Yoshihiro Sakoda & Hiroshi Kida

  4. Department of Cell and Molecular Biology, Chemical Physiology and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA

    Ryan McBride, Robert P. de Vries, Wenjie Peng & James C. Paulson

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  1. Takahiro Hiono
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Correspondence to Hiroshi Kida.

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Hiono, T., Okamatsu, M., Igarashi, M. et al. Amino acid residues at positions 222 and 227 of the hemagglutinin together with the neuraminidase determine binding of H5 avian influenza viruses to sialyl Lewis X. Arch Virol 161, 307–316 (2016). https://doi.org/10.1007/s00705-015-2660-3

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