scholarly journals Functional and Structural Characterization of P[19] Rotavirus VP8* Interaction with Histo-blood Group Antigens

2016 ◽  
Vol 90 (21) ◽  
pp. 9758-9765 ◽  
Author(s):  
Xiaoman Sun ◽  
Dandi Li ◽  
Ruchao Peng ◽  
Nijun Guo ◽  
Miao Jin ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Blood Group ◽  
Cell Attachment ◽  
Specific Binding ◽  
Structural Characteristics ◽  
Structural Alignment ◽  
Specific Cell ◽  
Blood Group Antigens ◽  
Dependent Manner ◽  
Porcine Origin

ABSTRACT Rotaviruses (RVs) of species A (RVA) are a major causative agent of acute gastroenteritis. Recently, histo-blood group antigens (HBGAs) have been reported to interact with human RVA VP8* proteins. Human P[19] is a rare P genotype of porcine origin that infects humans sporadically. The functional and structural characteristics of P[19] VP8* interaction with HBGAs are unknown. In this study, we expressed and purified the VP8* proteins of human and porcine P[19] RVs. In oligosaccharide and saliva binding assays, P[19] VP8* proteins showed obvious binding to A-, B-, and O-type saliva samples irrespective of the secretor status, implying broad binding patterns. However, they did not display specific binding to any of the oligosaccharides tested. In addition, we solved the structure of human P[19] VP8* at 2.4 Å, which revealed a typical galectin-like fold. The structural alignment demonstrated that P[19] VP8* was most similar to that of P[8], which was consistent with the phylogenetic analysis. Structure superimposition revealed the basis for the lack of binding to the oligosaccharides. Our study indicates that P[19] RVs may bind to other oligosaccharides or ligands and may have the potential to spread widely among humans. Thus, it is necessary to place the prevalence and evolution of P[19] RVs under surveillance. IMPORTANCE Human P[19] is a rare P genotype of porcine origin. Based on phylogenetic analysis of VP8* sequences, P[19] was classified in the P[II] genogroup, together with P[4], P[6], and P[8], which have been reported to interact with HBGAs in a genotype-dependent manner. In this study, we explored the functional and structural characteristics of P[19] VP8* interaction with HBGAs. P[19] VP8* showed binding to A-, B-, and O-type saliva samples, as well as saliva of nonsecretors. This implies that P[19] has the potential to spread among humans with a broad binding range. Careful attention should be paid to the evolution and prevalence of P[19] RVs. Furthermore, we solved the structure of P[19] VP8*. Structure superimposition indicated that P[19] may bind to other oligosaccharides or ligands using potential binding sites, suggesting that further investigation of the specific cell attachment factors is warranted.

scholarly journals Norovirus and Histo-Blood Group Antigens: Demonstration of a Wide Spectrum of Strain Specificities and Classification of Two Major Binding Groups among Multiple Binding Patterns

2005 ◽  
Vol 79 (11) ◽  
pp. 6714-6722 ◽  
Author(s):  
Pengwei Huang ◽  
Tibor Farkas ◽  
Weiming Zhong ◽  
Ming Tan ◽  
Scott Thornton ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Blood Group ◽  
Acute Gastroenteritis ◽  
Specific Binding ◽  
Wide Spectrum ◽  
Phylogenetic Analyses ◽  
Lewis Antigens ◽  
Blood Group Antigens ◽  
Multiple Binding

ABSTRACT Noroviruses, an important cause of acute gastroenteritis, have been found to recognize human histo-blood group antigens (HBGAs) as receptors. Four strain-specific binding patterns to HBGAs have been described in our previous report. In this study, we have extended the binding patterns to seven based on 14 noroviruses examined. The oligosaccharide-based assays revealed additional epitopes that were not detected by the saliva-based assays. The seven patterns have been classified into two groups according to their interactions with three major epitopes (A/B, H, and Lewis) of human HBGAs: the A/B-binding group and the Lewis-binding group. Strains in the A/B binding group recognize the A and/or B and H antigens, but not the Lewis antigens, while strains in the Lewis-binding group react only to the Lewis and/or H antigens. This classification also resulted in a model of the norovirus/HBGA interaction. Phylogenetic analyses showed that strains with identical or closely related binding patterns tend to be clustered, but strains in both binding group can be found in both genogroups I and II. Our results suggest that noroviruses have a wide spectrum of host range and that human HBGAs play an important role in norovirus evolution. The high polymorphism of the human HBGA system, the involvement of multiple epitopes, and the typical protein/carbohydrate interaction between norovirus VLPs and HBGAs provide an explanation for the virus-ligand binding diversities.

scholarly journals Molecular basis of P[6] and P[8] major human rotavirus VP8* domain interactions with histo-blood group antigens

2019 ◽  
Author(s):  
Shenyuan Xu ◽  
Yang Liu ◽  
Ming Tan ◽  
Weiming Zhong ◽  
Dandan Zhao ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Blood Group ◽  
Molecular Basis ◽  
Disease Burden ◽  
Binding Domain ◽  
Specific Cell ◽  
Blood Group Antigens ◽  
Nuclear Magnetic

AbstractInitial cell attachment of rotavirus (RV) to specific cell surface glycans, which is the essential first step in RV infection, is mediated by the VP8* domain of the spike protein VP4. Recently, human histo-blood group antigens (HBGAs) have been identified as ligands or receptors for human RV strains. RV strains in the P[4] and P[8] genotypes of the P[II] genogroup share common recognition of the Lewis b and H type 1 antigens, while P[6], which is one of the other genotypes in P[II], only recognizes the H type 1 antigen. The molecular basis of receptor recognition by the major human P[8] RVs remains unknown due to lack of experimental structural information. Here, we used nuclear magnetic resonance (NMR) titration experiments and NMR-derived high ambiguity driven docking (HADDOCK) methods to elucidate the molecular basis for P[8] VP8* recognition of the Leb and type 1 HBGAs and for P[6] recognition of H type 1 HBGAs. Unlike P[6] VP8* that recognizes H type 1 HGBAs in a binding surface composed of an α-helix and a β-sheet, referred as “βα binding domain”, the P[8] VP8* binds the type 1 HBGAs requiring the presence of the Lewis epitope in a previously undescribed pocket formed by two β-sheets, referred as “ββ binding domain”. The observation that P[6] and P[8] VP8* domains recognize different glycan structures at distinct binding sites supports the hypothesis that RV evolution is driven, at least in part, by selective pressure driven adaptation to HBGA structural diversity of their natural hosts living in the world. Recognition of the role that HBGAs play in driving RV evolution is essential to understanding RV diversity, host ranges, disease burden and zoonosis and to developing strategies to improve vaccines against RV infections.Author summaryRotaviruses (RV)s are the main cause of severe diarrhea in humans and animals. Significant advances in understanding RV diversity, evolution and epidemiology have been made after discovering that RVs recognize histo-blood group antigens (HBGAs) as host cell receptors. While different RV strains are known to have distinct binding preferences for HBGA receptors, the molecular basis in controlling strain-specific host ranges remains unclear. In this study, we used solution nuclear magnetic resonance to determine the molecular level details for interactions of the human P[8] and P[6] RV VP8* domains with their HBGA receptors. The distinct binding patterns observed between these major human RVs and their respective receptor ligands provides insight into the evolutionary relationships between different P[II] genotypes that ultimately determine host ranges, disease burden, zoonosis and epidemiology, which may impact future strategies for vaccine development against RVs.

scholarly journals Histo-Blood Group Antigens Act as Attachment Factors of Rabbit Hemorrhagic Disease Virus Infection in a Virus Strain-Dependent Manner

2011 ◽  
Vol 7 (8) ◽  
pp. e1002188 ◽  
Author(s):  
Kristina Nyström ◽  
Ghislaine Le Gall-Reculé ◽  
Paola Grassi ◽  
Joana Abrantes ◽  
Nathalie Ruvoën-Clouet ◽  
...  
Keyword(s):  
Virus Infection ◽  
Disease Virus ◽  
Blood Group ◽  
Virus Strain ◽  
Rabbit Hemorrhagic Disease Virus ◽  
Hemorrhagic Disease ◽  
Blood Group Antigens ◽  
Dependent Manner ◽  
Rabbit Hemorrhagic Disease ◽  
Strain Dependent

scholarly journals Human Norovirus Histo-Blood Group Antigen (HBGA) Binding Sites Mediate the Virus Specific Interactions with Lettuce Carbohydrates

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 833
Author(s):  
Malak A. Esseili ◽  
Xiang Gao ◽  
Patricia Boley ◽  
Yixuan Hou ◽  
Linda J. Saif ◽  
...  
Keyword(s):  
Blood Group ◽  
Binding Sites ◽  
Specific Binding ◽  
Blood Group Antigen ◽  
Blood Group Antigens ◽  
Specific Interactions ◽  
Wild Type ◽  
Human Norovirus ◽  
Virus Like Particles ◽  
Foodborne Outbreaks

Lettuce is often implicated in human norovirus (HuNoV) foodborne outbreaks. We identified H-like histo-blood group antigens (HBGAs) on lettuce leaves as specific binding moieties for virus-like particles (VLPs) of HuNoV GII.4/HS194/2009 strain. The objective of this study was to determine whether HuNoV-lettuce binding is mediated through the virus HBGA binding sites (HBS). Toward this objective, VLPs of historical HuNoV GII.4 strains (1987, 1997, 2002, 2004 and 2006) with known natural mutations in their HBS, two newly generated VLP mutants of GII.4/HS194/2009 (D374A and G443A) and a VLP mutant (W375A) of GI.1/Norwalk/1968 along with its wild type VLPs, which displays distinct HBS, were investigated for their binding to lettuce. ELISA revealed that historical GII.4 strains binding to lettuce was dependent on their HBGAs profiles. The VLP mutants D374A and G443A lost binding to HBGAs and displayed no to minimal binding to lettuce, respectively. The VLPs of GI.1/Norwalk/1968 strain bound to lettuce through an H-like HBGA and the binding was inhibited by fucosidase digestion. Mutant W375A which was previously shown not to bind to HBGAs, displayed significantly reduced binding to lettuce. We conclude that the binding of HuNoV GII.4 and GI.1 strains to lettuce is mediated through the virus HBS.

The epidermal growth factor–like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans

Blood ◽  
2003 ◽  
Vol 102 (8) ◽  
pp. 2916-2924 ◽  
Author(s):  
Martin Stacey ◽  
Gin-Wen Chang ◽  
John Q. Davies ◽  
Mark J. Kwakkenbos ◽  
Ralph D. Sanderson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Chondroitin Sulfate ◽  
Cell Lines ◽  
Cell Attachment ◽  
Chinese Hamster ◽  
Specific Cell ◽  
Dependent Manner ◽  
Ligand Interaction ◽  
Epidermal Growth

Abstract Using multivalent protein probes, an evolutionarily conserved endogenous ligand for EMR2, a human myeloid cell–restricted EGF-TM7 receptor, was identified on the surface of a number of adherent cell lines. In addition, in situ staining of the ligand has revealed specific in vivo patterns consistent with a connective tissue distribution. The interaction is conserved across species and mediated exclusively by the largest EMR2 isoform containing 5 epidermal growth factor (EGF)–like modules. Antibody-blocking studies subsequently revealed that the fourth EGF-like module constitutes the major ligand-binding site. The largest isoform of CD97, a related EGF-TM7 molecule containing an identical EGF-like module, also binds to the putative EMR2 ligand. Through the use of mutant Chinese hamster ovary (CHO) cell lines defective in glycosaminoglycans (GAGs) biosynthesis as well as the enzymatic removal of specific cell surface GAGs, the molecular identity of the EMR2 ligand was identified as chondroitin sulfate (CS). Thus, exogenous CS GAGs blocked the EMR2-ligand interaction in a dose-dependent manner. EMR2-CS interaction is Ca2+- and sulphation-dependent and results in cell attachment. This is the first report of a GAG ligand for the TM7 receptors extending the already vast repertoire of stimuli of the GPCR superfamily.

scholarly journals Studies on cell adhesion and recognition. I. Extent and specificity of cell adhesion triggered by carbohydrate-reactive proteins (glycosidases and lectins) and by fibronectin.

1981 ◽  
Vol 88 (1) ◽  
pp. 127-137 ◽  
Author(s):  
H Rauvala ◽  
W G Carter ◽  
S I Hakomori
Keyword(s):  
Cell Adhesion ◽  
Cell Attachment ◽  
Specific Binding ◽  
Specific Cell ◽  
Glycosidase Inhibitors ◽  
Acetylneuraminic Acid ◽  
Specific Binding Sites ◽  
High Concentrations ◽  
Coated Surfaces ◽  
Beta Galactosidase

The extent and the specificity of the initial cell attachment induced by various proteins coated on plastic surfaces have been studied with the following results: (a) Cell adhesion on the surfaces coated with sialidase and beta-galactosidase was as strong as on concanavalin A and limulus lectin-coated surfaces and the reactions were strongly inhibited by glycosidase inhibitors or by competitive substrates. The adhesion on sialidase was inhibited by 2-deoxy-2,3-dehydro-N-acetylneuraminic acid and by polysialoganglioside (GT1b) at low concentration (0.05-0.1 mM). The cell adhesion on beta-galactosidase coat was inhibited by 1,4-D-galactonolactone and beta-methylgalactoside but not by alpha-methylgalactoside. Thus, the initiation of cell adhesion on glycosidase surfaces could be mediated through the interactions of the specific binding sites of the enzyme surface with the cell surface substrates under physiological conditions. (b) Cell adhesion on various lectins could be blocked by various competing monosaccharides at the concentrations similar to the inhibitory concentrations for binding of lectins from solution to the cells. (c) Cell adhesion on fibronectin surfaces as well as on gelatin-coated surfaces was equally inhibited by GT1b at relatively high concentrations (0.25-0.5 mM). Lower concentrations of GT1b (0.05-0.1 mM) inhibited the cell adhesion on surfaces of Limulus lectin and sialidase. It is suggested that the cell adhesion mediated by fibronectin is based on yet unknown interactions in contrast to a specific cell adhesion through glycosidases and lectins.

scholarly journals Glycan-Induced Protein Dynamics in Human Norovirus P Dimers Depend on Virus Strain and Deamidation Status

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2125
Author(s):  
Jasmin Dülfer ◽  
Hao Yan ◽  
Maxim N. Brodmerkel ◽  
Robert Creutznacher ◽  
Alvaro Mallagaray ◽  
...  
Keyword(s):  
Protein Dynamics ◽  
Cell Attachment ◽  
High Specificity ◽  
Structural Similarity ◽  
Viral Gastroenteritis ◽  
Blood Group Antigens ◽  
Dependent Manner ◽  
Exchange Mass Spectrometry ◽  
Different Strains ◽  
Strain Dependent

Noroviruses are the major cause of viral gastroenteritis and re-emerge worldwide every year, with GII.4 currently being the most frequent human genotype. The norovirus capsid protein VP1 is essential for host immune response. The P domain mediates cell attachment via histo blood-group antigens (HBGAs) in a strain-dependent manner but how these glycan-interactions actually relate to cell entry remains unclear. Here, hydrogen/deuterium exchange mass spectrometry (HDX-MS) is used to investigate glycan-induced protein dynamics in P dimers of different strains, which exhibit high structural similarity but different prevalence in humans. While the almost identical strains GII.4 Saga and GII.4 MI001 share glycan-induced dynamics, the dynamics differ in the emerging GII.17 Kawasaki 308 and rare GII.10 Vietnam 026 strain. The structural aspects of glycan binding to fully deamidated GII.4 P dimers have been investigated before. However, considering the high specificity and half-life of N373D under physiological conditions, large fractions of partially deamidated virions with potentially altered dynamics in their P domains are likely to occur. Therefore, we also examined glycan binding to partially deamidated GII.4 Saga and GII.4 MI001 P dimers. Such mixed species exhibit increased exposure to solvent in the P dimer upon glycan binding as opposed to pure wildtype. Furthermore, deamidated P dimers display increased flexibility and a monomeric subpopulation. Our results indicate that glycan binding induces strain-dependent structural dynamics, which are further altered by N373 deamidation, and hence hint at a complex role of deamidation in modulating glycan-mediated cell attachment in GII.4 strains.

scholarly journals The P Domain of Norovirus Capsid Protein Forms Dimer and Binds to Histo-Blood Group Antigen Receptors

2004 ◽  
Vol 78 (12) ◽  
pp. 6233-6242 ◽  
Author(s):  
Ming Tan ◽  
Rashmi S. Hegde ◽  
Xi Jiang
Keyword(s):  
Blood Group ◽  
Specific Binding ◽  
Expression System ◽  
Essential Elements ◽  
Site Directed Mutagenesis ◽  
High Yield ◽  
Receptor Interaction ◽  
Blood Group Antigens ◽  
Donor Strain ◽  
P Domain

ABSTRACT Noroviruses (NVs) are the most important pathogen of epidemic nonbacterial gastroenteritis. The recent finding that NVs recognize human histo-blood group antigens (HBGAs) as receptors provided a new approach to study the pathogenesis of NVs. Using computational and site-directed mutagenesis approaches, our investigators previously identified a plausible binding pocket in the P domain of the NV capsids. In this study, we further characterize the role of the P domain in the interaction with human HBGA receptors using three NV strains representing three binding patterns. Our results show that the isolated P domain, although it did not form virus-like particles (VLPs), formed dimers, and the dimers bound HBGAs with the same patterns as those of the intact viral capsids. In contrast, the S domain, which formed small, thin-layer VLPs, did not bind A, B, or H HBGAs. A chimera containing the S domain of VA387 and the P domain of MOH revealed a binding pattern of the P donor strain (MOH). Deletion experiments revealed that an intact P domain is necessary for receptor binding. The P domain dimers are stable over a broad range of pH (2 to 11) or under strong denaturing conditions. Taken together, our results suggest that the P domain of NV contains essential elements for strain-specific binding to receptors. Further study of the P domain will provide useful information about the virus-receptor interaction. The high yield and easy production of the recombinant P protein in the Escherichia coli expression system will provide a simple approach to this goal.

scholarly journals Glycan-induced protein dynamics in human norovirus P dimers depend on virus strain and deamidation status

2020 ◽  
Author(s):  
Jasmin Dülfer ◽  
Hao Yan ◽  
Maxim N Brodmerkel ◽  
Robert Creutznacher ◽  
Alvaro Mallagaray ◽  
...  
Keyword(s):  
Protein Dynamics ◽  
Cell Attachment ◽  
Structural Similarity ◽  
Blood Group Antigens ◽  
Dependent Manner ◽  
Exchange Mass Spectrometry ◽  
High Structural Similarity ◽  
Capsid Protein Vp1 ◽  
Different Strains ◽  
Strain Dependent

AbstractNoroviruses are the major cause of gastroenteritis and re-emerge worldwide every year, with GII.4 currently being the most frequent human genotype. The norovirus capsid protein VP1 is essential for host immune response. The P domain mediates cell attachment via histo blood-group antigens (HBGAs) in a strain-dependent manner but how these glycan-interactions actually relate to cell entry remains unclear. Here, hydrogen/deuterium exchange mass spectrometry (HDX-MS) is used to investigate glycan-induced protein dynamics in P dimers of different strains, which exhibit high structural similarity but different prevalence in humans. While the almost identical strains GII.4 Saga and GII.4 MI001 share glycan-induced dynamics, the dynamics differ in the emerging GII.17 Kawasaki 308 and rare GII.10 Vietnam 026 strain. We also further examine structural effects of N373 deamidation upon glycan binding in partially deamidated GII.4 P dimers, which are likely present during infection. Such mixed species exhibit increased exposure to solvent in the P dimer upon glycan binding as opposed to pure wildtype. Furthermore, deamidated P dimers display increased flexibility and a monomeric population. Our results indicate that glycan binding induces strain-dependent structural dynamics, which are further altered by N373 deamidation, and hence hint at a role of deamidation in modulating cell attachment and entry in GII.4 strains.

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