Qualitative and Quantitative Analysis of the Binding of GII.4 Norovirus Variants onto Human Blood Group Antigens

Rougemont, Alexis de; Ruvoën-Clouet, Nathalie; Benoit, Sandrine; Estienney, Marie; Élie-Caille, Céline; Aho, Serge; Pothier, Pierre; Pendu, Jacques Le; Boireau, Wilfrid; Belliot, Gaël

doi:10.1128/jvi.02077-10

Cited by 131 publications

(176 citation statements)

References 50 publications

(74 reference statements)

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“…Despite the discovery of human norovirus nearly 40 years ago (27), little is known about the capsid interaction with ligands (18,44) other than HBGAs (8,11,12,15,21,45). Our finding that citrate binds at the terminal fucose binding site was somewhat unexpected, given that the structure of citrate is unlike the structure of fucose and considering that the GII.10 P domain could not bind HBGAs having an ␣-fucose1-3/4 saccharide (21).…”

Section: Discussioncontrasting

confidence: 43%

“…Most studies agreed that a dominant GII.4 norovirus was replaced the following year or next by a new GII.4 "variant" norovirus that had ϳ5% amino acid change in the capsid gene (6,9,10,30,31,47). The reason that the GII.4 variants dominated and not some other genotype was unknown, but studies have shown specific mutations at or surrounding the HBGA binding site were capable of altering the HBGA binding patterns (15,30,31,52). These small changes were thought to lead to new GII.4 variants capable of causing pandemics, analogous to influenza A virus evolution (14,29).…”

Section: Discussionmentioning

confidence: 99%

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Structural Basis for Norovirus Inhibition and Fucose Mimicry by Citrate

Hansman

Shahzad‐ul‐Hussan

McLellan

et al. 2012

J Virol

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Human noroviruses bind with their capsid-protruding domains to histo-blood-group antigens (HBGAs), an interaction thought to direct their entry into cells. Although human noroviruses are the major cause of gastroenteritis outbreaks, development of antivirals has been lacking, mainly because human noroviruses cannot be cultivated. Here we use X-ray crystallography and saturation transfer difference nuclear magnetic resonance (STD NMR) to analyze the interaction of citrate with genogroup II (GII) noroviruses. Crystals of citrate in complex with the protruding domain from norovirus GII.10 Vietnam026 diffracted to 1.4 Å and showed a single citrate bound at the site of HBGA interaction. The citrate interaction was coordinated with a set of capsid interactions almost identical to that involved in recognizing the terminal HBGA fucose, the saccharide which forms the primary conserved interaction between HBGAs and GII noroviruses. Citrate and a water molecule formed a ring-like structure that mimicked the pyranoside ring of fucose. STD NMR showed the protruding domain to have weak affinity for citrate (460 M). This affinity, however, was similar to the affinities of the protruding domain for fucose (460 M) and H type 2 trisaccharide (390 M), an HBGA shown previously to be specifically recognized by human noroviruses. Importantly, competition STD NMR showed that citrate could compete with HBGA for norovirus binding. Together, the results suggest that citrate and other glycomimetics have the potential to block human noroviruses from binding to HBGAs.H uman noroviruses, family Caliciviridae, are the dominant cause of outbreaks of gastroenteritis. Many aspects of human norovirus replication, however, remain unclear, mainly because these viruses cannot be grown in cell culture. Transmission predominately occurs through ingestion of contaminated foods, airborne transmission, and person-to-person contact. Medical treatment usually involves orally administered fluids and electrolyte replacement therapy. Currently, there is no effective vaccine.Human noroviruses can be divided into 2 main genogroups (GI and GII), which can be further subdivided into at least 25 different genotypes (GI.1 to -8 and GII.1 to -17) (26, 57). The norovirus genome has three open reading frames (ORFs) that encode nonstructural, capsid, and small structural proteins, respectively. The capsid of human norovirus is composed of two domains, shell and protruding (P) domains. The shell forms a scaffold around the RNA, and the dimeric P domain contains determinants for both antigenicity and receptor binding (25,43,51). The P domain is further subdivided into P1 and P2 subdomains, where the P1 subdomain interacts with the shell domain and is buried under the outermost P2 subdomain.Human noroviruses bind to histo-blood group antigens (HBGAs), with recognition occurring in the P domain. HBGAs are complex carbohydrates present on mucosal epithelial cells or free antigens in blood, saliva, and other fluids (32). X-ray crystal structures of norovirus P domains in com...

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Section: Discussioncontrasting

confidence: 43%

Section: Discussionmentioning

confidence: 99%

Structural Basis for Norovirus Inhibition and Fucose Mimicry by Citrate

Hansman

Shahzad‐ul‐Hussan

McLellan

et al. 2012

J Virol

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“…Utilizing MAbs rather than polyclonal sera for detection increased the assay sensitivity enough to detect lower levels of biotinylated-HBGA binding. As has been demonstrated repeatedly, one amino acid difference within the P2 domain can significantly alter VLP-HBGA affinity (13,15,29); therefore, making comparisons between data sets is misleading without the accompanying P2 subdomain sequence information.…”

Section: Figmentioning

confidence: 99%

“…P2 represents the most exposed polypeptide on the surface of the viral particle and determines its interactions with potential neutralizing antibodies and with histo-blood group antigens (HBGAs) (10,12,28,29,32). The P2 domain of the major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered ligand binding properties and antigenicity (1,5,7,15,29,41,43).…”

mentioning

confidence: 99%

Monoclonal Antibody-Based Antigenic Mapping of Norovirus GII.4-2002

Lindesmith

Debbink

Swanstrom

et al. 2012

J Virol

116

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Noroviruses are the primary cause of epidemic gastroenteritis in humans, and GII.4 strains cause ϳ80% of the overall disease burden. Surrogate neutralization assays using sera and mouse monoclonal antibodies (MAbs) suggest that antigenic variation maintains GII.4 persistence in the face of herd immunity, as the emergence of new pandemic strains is accompanied by newly evolved neutralization epitopes. To potentially identify specific blockade epitopes that are likely neutralizing and evolving between pandemic strains, mice were hyperimmunized with GII.

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“…The mechanisms that have driven the fitness of this variant have not been established completely, but a number of mutations in ORF1 and ORF2 have been detected and studied extensively. Interestingly, this strain presented a unique amino acid (aa) insertion (Gly394) in the P2 domain that was in close proximity to the HBGA binding site (9) and altered the binding of VLPs to synthetic carbohydrates (12,39).…”

mentioning

confidence: 99%