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Inhibition of H5N1 highly pathogenic influenza virus by suppressing a specific sialyltransferase

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Abstract

Avian influenza viruses preferentially use α2,3-linked sialic acid as a receptor for binding and entry into target cells. The sialic acid is the terminal residue of various types of glycan. There are two major types of α2,3-linked sialic acid differing in the penultimate bond: Neu5Acα2-3Galβ1-3GalNAc and Neu5Acα2-3Galβ1-4GlcNAc. In the human airway, while Neu5Acα2-3Galβ1-3GalNAc is present only in alveolar epithelial cells, the Neu5Acα2-3Galβ1-4GlcNAc is expressed in both the upper and lower airway. Previous data showed preferential binding of hemagglutinin from H5N1 highly pathogenic influenza virus to Neu5Acα2-3Galβ1-4GlcNAc. We further show here that suppression of this sialic acid by siRNA against a sialyltransferase, ST3GAL4, can inhibit H5N1 avian influenza virus infection and that this gene is abundantly expressed in human pharynx, trachea and bronchus. These data suggest that the ST3GAL4 gene is responsible for biosynthesis of the viral receptor and may play a crucial role in infection of H5N1 avian influenza virus in humans.

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Acknowledgments

Y.M. was supported by the Mahidol Medical Scholar Program. O.S. and C.B. were supported by the postdoctoral and research assistant program of the Faculty of Medicine Siriraj Hospital. The project was supported by a research grant from Thailand Research Fund.

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Authors and Affiliations

  1. Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand

    Yuwarat Monteerarat

  2. Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand

    Ornpreya Suptawiwat, Chompunuch Boonarkart & Prasert Auewarakul

  3. Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand

    Mongkol Uiprasertkul

  4. Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand

    Vip Viprakasit

Authors
  1. Yuwarat Monteerarat
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  2. Ornpreya Suptawiwat
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  3. Chompunuch Boonarkart
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  4. Mongkol Uiprasertkul
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  5. Prasert Auewarakul
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  6. Vip Viprakasit
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Correspondence to Prasert Auewarakul or Vip Viprakasit.

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Monteerarat, Y., Suptawiwat, O., Boonarkart, C. et al. Inhibition of H5N1 highly pathogenic influenza virus by suppressing a specific sialyltransferase. Arch Virol 155, 889–893 (2010). https://doi.org/10.1007/s00705-010-0658-4

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  • DOI: https://doi.org/10.1007/s00705-010-0658-4

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