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Sialic acid dependence in rotavirus host cell invasion

Nature Chemical Biology volume 5, pages 91–93 (2009)Cite this article

Abstract

We used NMR spectroscopy, molecular modeling and infectivity competition assays to investigate the key interactions between the spike protein (VP8*) from 'sialidase-insensitive' human Wa and 'sialidase-sensitive' porcine CRW-8 rotaviruses and the glycans of gangliosides GM1 and GD1a. Our data provide strong evidence that N-acetylneuraminic acid is a key determinant for binding of these rotaviruses. This is in contrast to the widely accepted paradigm that sialic acids are irrelevant in host cell recognition by sialidase-insensitive rotaviruses.

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Figure 1: 1H NMR investigation of 2 and 3 in complex with rotavirus VP8*.
Figure 2: Analyses of cell binding and infection by rotaviruses Wa and CRW-8.

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Acknowledgements

We thank K. Hidari (University of Shizuoka) for the gift of GD1a, A. Bugarcic (Griffith University) and M. Kraschnefski (Griffith University) for preparation of Wa VP8* protein, and A. Szyczew (Griffith University) for production of Neu5Acα2Me. B.S.C., M.J.K., H.B. and M.v.I. gratefully acknowledge the financial support of the Australian Research Council (ARC). B.S.C. thanks the National Health and Medical Research Council of Australia (NHMRC) for the award of a Senior Research Fellowship. M.v.I. thanks the ARC for the award of an Australian Federation Fellowship and the NHMRC for financial support.

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Authors and Affiliations

  1. Institute for Glycomics, Gold Coast Campus, Griffith University, Parklands Drive, Southport, 4222, Queensland, Australia

    Thomas Haselhorst, Jeffrey C Dyason, Regan D Hartnell, Xing Yu, Milton J Kiefel, Helen Blanchard & Mark von Itzstein

  2. Department of Microbiology and Immunology, The University of Melbourne, Royal Parade, Parkville, 3010, Victoria, Australia

    Fiona E Fleming, Gavan Holloway, Kim Santegoets & Barbara S Coulson

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  1. Thomas Haselhorst
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Correspondence to Mark von Itzstein.

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Supplementary Figures 1–5, Supplementary Methods and Supplementary Discussion (PDF 8229 kb)

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Haselhorst, T., Fleming, F., Dyason, J. et al. Sialic acid dependence in rotavirus host cell invasion. Nat Chem Biol 5, 91–93 (2009). https://doi.org/10.1038/nchembio.134

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