Fondness for sugars of enteric viruses confronts them with human glycans genetic diversity


Together, norovirus and rotavirus are responsible for the majority of gastroenteritis cases worldwide, leading to a large number of deaths of children in low-income countries. Both attach to glycans of the histo-blood group antigen type (HBGAs) widely expressed in the digestive tract of vertebrates, albeit with interspecies differences. In humans, their synthesis is performed by glycosyltransferases encoded by the highly polymorphic ABO, FUT2 and FUT3 genes that are under long-term balanced selection. The combination of functional and null or weak alleles at these loci provides a diversity of glycan structures that define the ABO, Secretor and Lewis phenotypes. At the initial stage of infection norovirus and rotavirus attach to these glycans, although distinct strains of each virus present different specificities for individual glycans, hence exhibiting preferences for different human phenotypes. Absence or low expression of the recognized glycan motifs due to genetic polymorphism is associated with resistance to the disease, showing that the HBGA polymorphisms provide a population-based innate protection. Epidemiologically dominant strains of either norovirus or rotavirus display specificity for glycan motifs present in large fractions of the population, which may differ between geographical areas in accordance with the frequency of the ABO, FUT2, FUT3 gene polymorphisms. Evidence for virus adaptation to these geographical differences is amounting, indicative of a host–pathogen co-evolution and suggesting that enteric pathogens such as norovirus and rotavirus are likely the driving forces behind the balanced HBGA polymorphisms.

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The work of the authors’ laboratory on this topic was supported by Inserm (Institut National de la Santé et de la Recherche Médicale), the Région des Pays de la Loire and ANR (Agence Nationale de la Recherche) through several grants. The authors are most grateful to the past and present members of the laboratory Séverine Marionneau, Maha Zakhour, Jézabel Rocher, Béatrice Le Moullac-Vaidye, Laure Barbé, Adrien Breiman, Amira Khachou and Tasnuva Ahmed for their outstanding contributions to the research presented in this review.

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Le Pendu, J., Ruvoën-Clouet, N. Fondness for sugars of enteric viruses confronts them with human glycans genetic diversity. Hum Genet (2019).

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