Histo-blood group antigen-binding specificities of human rotaviruses are associated with gastroenteritis but not with in vitro infection

Scientific Reports
Laure BarbéJacques Le Pendu

Abstract

Human strains of rotavirus A (RVAs) recognize fucosylated glycans belonging to histo-blood group antigens (HBGAs) through their spike protein VP8*. Lack of these ligands due to genetic polymorphisms is associated with resistance to gastroenteritis caused by P[8] genotype RVAs. With the aim to delineate the contribution of HBGAs in the process, we analyzed the glycan specificity of VP8* proteins from various P genotypes. Binding to saliva of VP8* from P[8] and P[4] genotypes required expression of both FUT2 and FUT3 enzymes, whilst binding of VP8* from the P[14] genotype required FUT2 and A enzymes. We further defined a glycan motif, GlcNAcβ3Galβ4GlcNAc, recognized by P[6] clinical strains. Conversion into Lewis antigens by the FUT3 enzyme impaired recognition, explaining their lower binding to saliva of Lewis positive phenotype. In addition, the presence of neutralizing antibodies was associated with the presence of the FUT2 wild type allele in sera from young healthy adults. Nonetheless, in vitro infection of transformed cell lines was independent of HBGAs expression, indicating that HBGAs are not human RV receptors. The match between results from saliva-based binding assays and the epidemiological data indicates that the poly...Continue Reading

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Citations

Nov 26, 2019·The Journal of Infectious Diseases·Karen BonifaceJulie E Bines
Jul 25, 2019·Current Opinion in Infectious Diseases·Sasirekha Ramani, Sidhartha Giri
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Mar 20, 2020·The Journal of Infectious Diseases·Amira KhachouJacques Le Pendu
Apr 13, 2019·Viruses·Raúl Pérez-OrtínJavier Buesa
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Methods Mentioned

BETA
flow cytometry
fluorescence microscopy
PCR
ion exchange chromatography
gel filtration
flow-cytometry

Software Mentioned

GraphPad Prism
FlowJo
ArrayScan
Rotarix
GraphPad
GeneART
RotaTeq

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