| 1. |
- Barbe, Laure, et al.
(författare)
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Histo-blood group antigen-binding specificities of human rotaviruses are associated with gastroenteritis but not with in vitro infection
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)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, GlcNAc beta 3Gal beta 4GlcNAc, 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 polymorphism of human HBGAs controls susceptibility to RVAs, although the exact mechanism remains unclear.
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| 2. |
- Le Pendu, Jacques, et al.
(författare)
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Host-pathogen co-evolution and glycan interactions
- 2014
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Ingår i: Current Opinion in Virology. - : Elsevier BV. - 1879-6257 .- 1879-6265. ; 7, s. 88-94
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Forskningsöversikt (refereegranskat)abstract
- Noroviruses and rotavirus A bind to polymorphic glycans of the histo-blood group type (HBGAs). Norovirus strains that bind to HBGAs can collectively infect all humans but each strain only infects a subgroup of the population, suggesting a past co-evolution that led to a trade-off where the human population is partly protected whilst the virus circulation is maintained. We termed 'Herd Innate Protection' the host species partial protection provided by the HBGAs polymorphism. Given its recent emergence, high virulence and HBGAs attachment, RHDV provides a model for studying calicivirus-host co-evolution. Field observations documented evolution of the virus ability to recognize the host HBGAs diversity and reciprocal strain-dependent selection of HBGA phenotypes following outbreaks, indicating host-pathogen co-evolution involving glycan polymorphisms.
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| 3. |
- Le Pendu, Jacques, et al.
(författare)
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Mendelian resistance to human norovirus infections
- 2006
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Ingår i: Seminars in Immunology. - : Elsevier BV. - 1044-5323 .- 1096-3618. ; 18:6, s. 375-386
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Tidskriftsartikel (refereegranskat)abstract
- Noroviruses have emerged as a major cause of acute gastroenteritis in humans of all ages. Despite high infectivity of the virus and lack of long-term immunity, volunteer and authentic studies has suggested the existence of inherited protective factors. Recent studies have shown that histo-blood group antigens (HBGAs) and in particular secretor status controlled by the α1,2fucosyltransferase FUT2 gene determine susceptibility to norovirus infections, with nonsecretors (FUT2-/-), representing 20% of Europeans, being highly resistant to symptomatic infections with major strains of norovirus. Moreover, the capsid protein from distinct strains shows different HBGA specificities, suggesting a host-pathogen co-evolution driven by carbohydrate-protein interactions. © 2006.
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| 4. |
- Rydell, Gustaf E, et al.
(författare)
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Human noroviruses recognize sialyl Lewis x neoglycoprotein. : Norovirus binding to SLex
- 2009
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 19:3, s. 309-20
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Tidskriftsartikel (refereegranskat)abstract
- The carbohydrate binding characteristics of a norovirus GII.3 (Chron1) and a GII.4 (Dijon) strain were investigated using virus-like particles (VLPs) and saliva samples from 81 individuals genotyped for FUT2 (secretor) and FUT3 (Lewis) and phenotyped for ABO and Lewis blood groups. The two VLPs showed a typical secretor-gene-dependent binding and bound significantly stronger to saliva from A, B, and AB than from O individuals (P < 0.0001 and P < 0.001) but did not bind to any samples from secretor-negative individuals. The GII.3 strain showed larger interindividual variation and bound stronger to saliva from B than from A(2) secretors (P < 0.01). When assaying for binding to neoglycoproteins, the GII.3 and GII.4 strains were compared with the Norwalk GI.1 prototype strain. Although all three strains bound to Lewis b (and H type 1 chain) glycoconjugates, only the two GII strains showed an additional binding to sialyl Lewis x. This novel binding was specific since the VLPs did not bind to structural analogs, e.g., Lewis x or sialyl Lewis a, but only to sialyl Lewis x, sialyl diLewis x and sialylated type 2 chain conjugates. In inhibition experiments, the sialyl Lewis x conjugate was the most potent inhibitor. The minimal requirement for this potential receptor structure is Neu5Ac alpha 3Gal beta 4(Fuc alpha 3)GlcNAc beta 3Gal beta- where Fuc is not absolutely necessary for binding. Our study shows that some human norovirus GII strains have at least two binding specificities: one secretor-gene-dependent related to alpha1,2-fucosylated carbohydrates and another related to alpha2,3-sialylated carbohydrates of the type 2 chain, e.g., sialyl Lewis x.
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| 5. |
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| 6. |
- Rydell, Gustaf E, et al.
(författare)
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Human noroviruses recognize sialyl Lewis x neoglycoprotein
- 2009
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 19:3, s. 309-320
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Tidskriftsartikel (refereegranskat)abstract
- The carbohydrate binding characteristics of a norovirus GII.3 (Chron1) and a GII.4 (Dijon) strain were investigated using virus-like particles (VLPs) and saliva samples from 81 individuals genotyped for FUT2 (secretor) and FUT3 (Lewis) and phenotyped for ABO and Lewis blood groups. The two VLPs showed a typical secretor-gene-dependent binding and bound significantly stronger to saliva from A, B, and AB than from O individuals (P < 0.0001 and P < 0.001) but did not bind to any samples from secretor-negative individuals. The GII.3 strain showed larger interindividual variation and bound stronger to saliva from B than from A(2) secretors (P < 0.01). When assaying for binding to neoglycoproteins, the GII.3 and GII.4 strains were compared with the Norwalk GI.1 prototype strain. Although all three strains bound to Lewis b (and H type 1 chain) glycoconjugates, only the two GII strains showed an additional binding to sialyl Lewis x. This novel binding was specific since the VLPs did not bind to structural analogs, e.g., Lewis x or sialyl Lewis a, but only to sialyl Lewis x, sialyl diLewis x and sialylated type 2 chain conjugates. In inhibition experiments, the sialyl Lewis x conjugate was the most potent inhibitor. The minimal requirement for this potential receptor structure is Neu5Ac alpha 3Gal beta 4(Fuc alpha 3)GlcNAc beta 3Gal beta- where Fuc is not absolutely necessary for binding. Our study shows that some human norovirus GII strains have at least two binding specificities: one secretor-gene-dependent related to alpha 1,2-fucosylated carbohydrates and another related to alpha 2,3-sialylated carbohydrates of the type 2 chain, e.g., sialyl Lewis x.
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