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The carbohydrate moiety and high molecular weight carrier of histo-blood group antigens are both required for norovirus-receptor recognition

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Abstract

Histo-blood group antigens (HBGAs) on human intestinal epithelium serve as receptors for noroviruses (NVs). These antigens also are expressed in milk and may act as decoy receptors to protect breast-fed infants and others against NV disease. In this study we demonstrated that human milk is highly variable in synthesis of HBGAs, which differs from that of saliva; a large quantity of small, soluble HBGAs are found in milk, but much less in saliva and are recognized by MAbs, but not by NVs. There is another group of HBGAs, of high MW, found in both milk and saliva, and recognized by both NVs and MAbs. These results suggest that the specificity of NVs and MAbs to HBGAs are different and the backbones in addition to the carbohydrate moiety are required for NV recognition. Further studies to define the structure and genetics of the high MW milk glycans are necessary.

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Abbreviations

NVs:

noroviruses

HBGAs:

histo-blood group antigens

FPLC:

fast protein liquid chromatography

MAb:

monoclonal antibody

TFMS:

trifluoromethanesulphonic acid

DTT:

dithiothreitol

mAU:

milliabsorbance unit

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Acknowledgements

We thank Weiming Zhong for laboratory assistance and David Newburg for scientific discussion in this manuscript. This study was supported by the NIH (R01 AI37093, R01 AI055649, DK40561, DK070250, and P01 HD 13021) and the Department of Defense (PR033018).

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Authors and Affiliations

  1. Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229-3039, USA

    Pengwei Huang & Xi Jiang

  2. Center for Epidemiology and Biostatistics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Ardythe L. Morrow

  3. College of Medicine, University of Cincinnati, Cincinnati, OH, USA

    Ardythe L. Morrow & Xi Jiang

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  1. Pengwei Huang
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  2. Ardythe L. Morrow
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  3. Xi Jiang
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Correspondence to Xi Jiang.

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Huang, P., Morrow, A.L. & Jiang, X. The carbohydrate moiety and high molecular weight carrier of histo-blood group antigens are both required for norovirus-receptor recognition. Glycoconj J 26, 1085–1096 (2009). https://doi.org/10.1007/s10719-009-9229-x

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