Skip to Main content Skip to Navigation
Theses

Rôle des antigènes tissulaires de groupes sanguins humains A, B, H et Lewis dans l'évolution des Norovirus GII.4

Abstract : Noroviruses are one of the leading causes of gastroenteritis worldwide. Since 2002 successive GII.4 variants have circulated in the population before being replaced every 2-3 years, which raises questions about the role of their histo-blood group antigen (HBGAs) receptors in their evolution. We analyzed the interaction between representative GII.4 variants and HBGAs and determined the role of selected amino acids (aa) in the binding profiles. By mutagenesis, we showed that there was a strict structural requirement for the aa directly implicated in HBGA bindings. The ablation of the threonine 395 residue, an epidemiological feature of the post 2002 variants, allowed to gain the capacity to bind to the Lewis x and sialyl-Lewis x antigens, demonstrating that aa residues outside the HBGA binding site can modify the binding properties. The analysis of the attachment of VLPs from 6 variants isolated from 1987 to 2007 to phenotyped saliva samples and synthetic HBGAs shows that all variants could attach to saliva of secretors irrespective of the ABO phenotype and to oligosaccharides characteristic of the secretor phenotype. Interestingly, two recent variants additionally bound to carbohydrates present in the saliva of Lewis-positive non-secretors. Our data suggest that GII.4 binding to Lex and Si-Lex antigens might be a by-product of the genetic variation of the aa located in the vicinity of the binding site. Analysis of the binding properties by surface plasmon resonance showed that only post 2002 variants presented a strong affinity for A and B antigens, suggesting that the GII.4 evolution could be related to an increased affinity for HBGAs for the post 2002 variants.
Complete list of metadatas

https://tel.archives-ouvertes.fr/tel-00739334
Contributor : Abes Star :  Contact
Submitted on : Monday, October 8, 2012 - 1:01:29 AM
Last modification on : Friday, October 23, 2020 - 4:49:04 PM
Long-term archiving on: : Wednesday, January 9, 2013 - 2:45:13 AM

File

these_A_DE_ROUGELONT_Alexis_20...
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-00739334, version 1

Collections

Citation

Alexis De Rougemont. Rôle des antigènes tissulaires de groupes sanguins humains A, B, H et Lewis dans l'évolution des Norovirus GII.4. Sciences agricoles. Université de Bourgogne, 2011. Français. ⟨NNT : 2011DIJOS029⟩. ⟨tel-00739334⟩

Share

Metrics

Record views

1605

Files downloads

7548