Lewis b antigen is a common ligand for genogroup I norovirus strains

Someya, Yuichi

doi:10.1002/2211-5463.13455

Cited by 2 publications

(3 citation statements)

References 41 publications

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“…To further characterize these antibody fragments, we investigated whether they inhibited the binding of VLPs to HBGAs. Here, we adopted an ELISA-based binding assay in which the Lewis b antigens are coated as ligands for VLPs, as described previously ( 20 ). In the presence of the CV-1A1 Fv-clasp or the CV-1A1 scFv, the binding of the Chiba VLPs to Lewis b antigens was inhibited dependent upon the concentration of antibody fragments added, but the binding of the Vancouver VLPs was never affected ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The GI.4 genotype has been one of the major genotypes in genogroup I for many years in Japan ( 7 ), and the Chiba strain, a prototype for GI.4, has thus been extensively studied ( 13 , 14 , 18 – 20 ). It is noteworthy that the GI.4 Chiba strain has recently been investigated as a bivalent vaccine candidate together with the GII.4 VLPs ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

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Structural analyses of the GI.4 norovirus by cryo-electron microscopy and X-ray crystallography revealing binding sites for human monoclonal antibodies

Kimura-Someya,

Katsura,

Kato-Murayama

et al. 2024

J Virol

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Noroviruses are major causative agents of acute nonbacterial gastroenteritis in humans. There are neither antiviral therapeutic agents nor vaccines for noroviruses at this time. To evaluate the potential usefulness of two previously isolated human monoclonal antibody fragments, CV-1A1 and CV-2F5, we first conducted a single-particle analysis to determine the cryo-electron microscopy structure of virus-like particles (VLPs) from the genogroup I genotype 4 (GI.4) Chiba strain uniformly coated with CV-1A1 fragments. The results revealed that the GI.4-specific CV-1A1 antibody bound to the P2 subdomain, in which amino acids are less conserved and variable. Interestingly, a part of the CV-1A1 intrudes into the histo-blood group antigen-binding site, suggesting that this antibody might exert neutralizing activity. Next, we determined the crystal structure of the protruding (P) domain of the capsid protein in the complex form with the CV-2F5 antibody fragment. Consistent with the cross-reactivity, the CV-2F5 bound to the P1 subdomain, which is rich in amino acids conserved among the GI strains, and moreover induced a disruption of Chiba VLPs. These results suggest that the broadly reactive CV-2F5 antibody can be used as both a universal detection reagent and an antiviral drug for GI noroviruses. IMPORTANCE We conducted the structural analyses of the VP1 protein from the GI.4 Chiba norovirus to identify the binding sites of the previously isolated human monoclonal antibodies CV-1A1 and CV-2F5. The cryo-electron microscopy of the Chiba virus-like particles (VLPs) complexed with the Fv-clasp forms of GI.4-specific CV-1A1 revealed that this antibody binds to the highly variable P2 subdomain, suggesting that this antibody may have neutralizing ability against the GI.4 strains. X-ray crystallography revealed that the CV-2F5 antibody bound to the P1 subdomain, which is rich in conserved amino acids. This result is consistent with the ability of the CV-2F5 antibody to react with a wide variety of GI norovirus strains. It is also found that the CV-2F5 antibody caused a disruption of VLPs. Our findings, together with previous reports on the structures of VP1 proteins and VLPs, are expected to open a path for the structure-based development of antivirals and vaccines against norovirus disease.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structural analyses of the GI.4 norovirus by cryo-electron microscopy and X-ray crystallography revealing binding sites for human monoclonal antibodies

Kimura-Someya,

Katsura,

Kato-Murayama

et al. 2024

J Virol

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“…The activity of FUT genes in relation to expression of HBGA (secretor-type Fucα1→2Gal modifications) and levels of Lewis antigens (Fucα1→3/4GlcNAc) are associated with norovirus infection (Nasir et al, 2012;Almand et al, 2017;Someya, 2022). Localization of P2 (the most variable region of the P protein containing the carbohydrate-binding motif) dimers on the viral particle surface has prompted intensive research because of potential interactions with branches of glycans.…”

Section: Norovirusesmentioning

confidence: 99%

Microbial lectome versus host glycolipidome: How pathogens exploit glycosphingolipids to invade, dupe or kill

Bereznicka¹,

Mikołajczyk²,

Czerwiński³

et al. 2022

Front. Microbiol.

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Glycosphingolipids (GSLs) are ubiquitous components of the cell membranes, found across several kingdoms of life, from bacteria to mammals, including humans. GSLs are a subclass of major glycolipids occurring in animal lipid membranes in clusters named “lipid rafts.” The most crucial functions of GSLs include signal transduction and regulation as well as participation in cell proliferation. Despite the mainstream view that pathogens rely on protein–protein interactions to survive and thrive in their hosts, many also target the host lipids. In particular, multiple pathogens produce adhesion molecules or toxins that bind GSLs. Attachment of pathogens to cell surface receptors is the initial step in infections. Many mammalian pathogens have evolved to recognize GSL-derived receptors. Animal glycosphingolipidomes consist of multiple types of GSLs differing in terminal glycan and ceramide structures in a cell or tissue-specific manner. Interspecies differences in GSLs dictate host specificity as well as cell and tissue tropisms. Evolutionary pressure exerted by pathogens on their hosts drives changes in cell surface glycoconjugates, including GSLs, and has produced a vast number of molecules and interaction mechanisms. Despite that abundance, the role of GSLs as pathogen receptors has been largely overlooked or only cursorily discussed. In this review, we take a closer look at GSLs and their role in the recognition, cellular entry, and toxicity of multiple bacterial, viral and fungal pathogens.

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Lewis b antigen is a common ligand for genogroup I norovirus strains

Cited by 2 publications

References 41 publications

Structural analyses of the GI.4 norovirus by cryo-electron microscopy and X-ray crystallography revealing binding sites for human monoclonal antibodies

Structural analyses of the GI.4 norovirus by cryo-electron microscopy and X-ray crystallography revealing binding sites for human monoclonal antibodies

Microbial lectome versus host glycolipidome: How pathogens exploit glycosphingolipids to invade, dupe or kill

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