Sulfated glycans containing NeuAcα2-3Gal facilitate the propagation of human H1N1 influenza A viruses in eggs

Tomomi Ichimiya; Masatoshi Okamatsu; Takaaki Kinoshita; Daiki Kobayashi; Osamu Ichii; Naoki Yamamoto; Yoshihiro Sakoda; Hiroshi Kida; Hiroto Kawashima; Kazuo Yamamoto; Sayaka Takase-Yoden; Shoko Nishihara

doi:10.1016/j.virol.2021.06.008

Sulfated glycans containing NeuAcα2-3Gal facilitate the propagation of human H1N1 influenza A viruses in eggs

Virology. 2021 Oct:562:29-39. doi: 10.1016/j.virol.2021.06.008. Epub 2021 Jun 25.

Authors

Affiliations

¹ Laboratory of Cell Biology, Department of Biosciences, Graduate School of Science and Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo, 192-8577, Japan.
² Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Kita 18-Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan.
³ Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18-Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan; Laboratory of Agrobiomedical Science, Faculty of Agriculture, Hokkaido University, Kita 9-Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan.
⁴ Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Kita 18-Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Kita 20-Nishi 10, Kita-ku, Sapporo, Hokkaido, 001-0020, Japan.
⁵ International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Kita 20-Nishi 10, Kita-ku, Sapporo, Hokkaido, 001-0020, Japan; International Institute for Zoonosis Control, Hokkaido University, Kita 20-Nishi 10, Kita-ku, Sapporo, Hokkaido, 001-0020, Japan.
⁶ Laboratory of Microbiology and Immunology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan.
⁷ Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba, 277-8562, Japan.
⁸ Laboratory of Virology, Department of Biosciences, Graduate School of Science and Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo, 192-8577, Japan; Glycan and Life Systems Integration Center (GaLSIC), Soka University, 1-236 Tangi-machi, Hachioji, Tokyo, 192-8577, Japan. Electronic address: takase@soka.ac.jp.
⁹ Laboratory of Cell Biology, Department of Biosciences, Graduate School of Science and Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo, 192-8577, Japan; Glycan and Life Systems Integration Center (GaLSIC), Soka University, 1-236 Tangi-machi, Hachioji, Tokyo, 192-8577, Japan. Electronic address: shoko@soka.ac.jp.

PMID: 34246113
DOI: 10.1016/j.virol.2021.06.008

Abstract

When human influenza viruses are isolated and passaged in chicken embryos, variants with amino acid substitutions around the receptor binding site of hemagglutinin (HA) are selected; however, the mechanisms that underlie this phenomenon have yet to be elucidated. Here, we analyzed the receptor structures that contributed to propagation of egg-passaged human H1N1 viruses. The analysis included seasonal and 2009 pandemic strains, both of which have amino acid substitutions of HA found in strains isolated or passaged in eggs. These viruses exhibited high binding to sulfated glycans containing NeuAcα2-3Gal. In MDCK cells overexpressing the sulfotransferase that synthesize Galβ1-4(SO₃^--6)GlcNAc, production of human H1N1 viruses was increased up to 90-fold. Furthermore, these sulfated glycans were expressed on the allantoic and amniotic membranes of chicken embryos. These results suggest that 6-sulfo sialyl Lewis X and/or NeuAcα2-3Galβ1-4(SO₃^--6)GlcNAc are involved in efficient propagation of human H1N1 viruses in chicken embryos.

Keywords: Egg-adaptation; Hemagglutinin; Influenza virus; Receptor; Sulfated glycan.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Allantois / metabolism
Amnion / metabolism
Animals
Carbohydrate Sulfotransferases
Chick Embryo / metabolism
Chick Embryo / virology*
Dogs
Galactosides / chemistry
Galactosides / metabolism
Hemagglutinin Glycoproteins, Influenza Virus / genetics
Hemagglutinin Glycoproteins, Influenza Virus / metabolism
Humans
Influenza A Virus, H1N1 Subtype / genetics
Influenza A Virus, H1N1 Subtype / growth & development*
Influenza A Virus, H1N1 Subtype / metabolism
Madin Darby Canine Kidney Cells
Mutation
N-Acetylneuraminic Acid / chemistry
N-Acetylneuraminic Acid / metabolism
Polysaccharides / chemistry
Polysaccharides / metabolism*
Receptors, Virus / metabolism
Sulfates / chemistry
Sulfates / metabolism*
Sulfotransferases / genetics
Sulfotransferases / metabolism

Substances

Galactosides
Hemagglutinin Glycoproteins, Influenza Virus
Polysaccharides
Receptors, Virus
Sulfates
hemagglutinin, human influenza A virus
Sulfotransferases
N-Acetylneuraminic Acid