Relevance of Host Cell Surface Glycan Structure for Cell Specificity of Influenza A Viruses

Markus Kastner; Andreas Karner; Rong Zhu; Qiang Huang; Andreas Geissner; Anne Sadewasser; Markus Lesch; Xenia Wörmann; Alexander Karlas; Peter H Seeberger; Thorsten Wolff; Peter Hinterdorfer; Andreas Herrmann; Christian Sieben

doi:10.3390/v15071507

Relevance of Host Cell Surface Glycan Structure for Cell Specificity of Influenza A Viruses

Viruses. 2023 Jul 5;15(7):1507. doi: 10.3390/v15071507.

Authors

Markus Kastner¹, Andreas Karner¹, Rong Zhu¹, Qiang Huang², Andreas Geissner^{3

4}, Anne Sadewasser⁵, Markus Lesch⁶, Xenia Wörmann⁶, Alexander Karlas⁶, Peter H Seeberger^{3

4}, Thorsten Wolff⁵, Peter Hinterdorfer¹, Andreas Herrmann⁷, Christian Sieben^{8

9}

Affiliations

¹ Institute for Biophysics, Johannes Kepler University Linz, 4020 Linz, Austria.
² State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University, Shanghai 200438, China.
³ Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, 14476 Potsdam, Germany.
⁴ Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
⁵ Division of Influenza and other Respiratory Viruses, Robert Koch-Institute, 13353 Berlin, Germany.
⁶ Molecular Biology Department, Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
⁷ Institut für Chemie und Biochemie, Freie Universität Berlin, Altensteinstraße 23a, 14195 Berlin, Germany.
⁸ Nanoscale Infection Biology Group, Department of Cell Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
⁹ Institute for Genetics, Technische Universität Braunschweig, 38106 Braunschweig, Germany.

Abstract

Influenza A viruses (IAVs) initiate infection via binding of the viral hemagglutinin (HA) to sialylated glycans on host cells. HA's receptor specificity towards individual glycans is well studied and clearly critical for virus infection, but the contribution of the highly heterogeneous and complex glycocalyx to virus-cell adhesion remains elusive. Here, we use two complementary methods, glycan arrays and single-virus force spectroscopy (SVFS), to compare influenza virus receptor specificity with virus binding to live cells. Unexpectedly, we found that HA's receptor binding preference does not necessarily reflect virus-cell specificity. We propose SVFS as a tool to elucidate the cell binding preference of IAVs, thereby including the complex environment of sialylated receptors within the plasma membrane of living cells.

Keywords: cell binding; force spectroscopy; influenza A virus.

Publication types

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

MeSH terms

Hemagglutinin Glycoproteins, Influenza Virus / chemistry
Humans
Influenza A virus* / metabolism
Influenza, Human*
Polysaccharides / chemistry
Receptors, Virus / metabolism
Virus Attachment

Substances

Receptors, Virus
Polysaccharides
Hemagglutinin Glycoproteins, Influenza Virus

Grants and funding

Q.H. was supported in part by the National Natural Science Foundation of China (31971377) and the Shanghai Natural Science Foundation (13ZR1402400). A.H. was supported by CRC 1449 “Dynamic Hydrogels at Biointerfaces” (DFG, German Research Foundation), Project ID 431232613–SFB 1449. R.Z. and P.H. were supported by Austrian Research Fund SFB-F35 and FWF project P35166. P.H.S and A.G. thank the Max-Planck Society for generous financial support. The work was further supported by grants from the German Ministry of Research and Education (BMBF) (e:Bio ViroSign, project 0316180D to T.W. and A.S.), as well as the German Research Foundation (DFG) (SFB 765 project C06 to T.W.). C.S. acknowledges support from the Helmholtz Association.