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.

scholarly journals Binding Patterns of Human Norovirus-Like Particles to Buccal and Intestinal Tissues of Gnotobiotic Pigs in Relation to A/H Histo-Blood Group Antigen Expression

2007 ◽  
Vol 81 (7) ◽  
pp. 3535-3544 ◽  
Author(s):  
S. Cheetham ◽  
M. Souza ◽  
R. McGregor ◽  
T. Meulia ◽  
Q. Wang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Blood Group ◽  
Hemagglutination Inhibition ◽  
Antigen Expression ◽  
Blood Group Antigen ◽  
Buccal Cells ◽  
Human Norovirus ◽  
Virus Like Particles ◽  
Hemagglutination Inhibition Test ◽  
Gnotobiotic Pigs

ABSTRACT Histo-blood group antigen (HBGA) phenotypes have been associated with susceptibility to human noroviruses (HuNoVs). Our aims were: (i) to determine the patterns of A/H HBGA expression in buccal and intestinal tissues of gnotobiotic (Gn) pigs; (ii) to determine if virus-like particles (VLPs) of HuNoV genogroup I (GI) and GII bind to A- or H-type tissues; (iii) to compare A/H expression and VLP binding patterns and confirm their binding specificities by blocking assays; (iv) to develop a hemagglutination inhibition test using buccal cells from live pigs to determine the Gn pig's A/H phenotype and to match viral strains with previously determined HuNoV VLP binding specificities; and (v) to determine the A/H phenotypes and compare these data to the infection outcomes of a previous study of 65 Gn pigs inoculated with HuNoV GII/4 strain HS66 and expressing A and/or H or neither antigen on their buccal and intestinal tissues (S. Cheetham, M. Souza, T. Meulia, S. Grimes, M. G. Han, and L. J. Saif, J. Virol. 80:10372-10381, 2006). We found that the HuNoV GI/GII VLPs of different clusters bound to tissues from four pigs tested (two A+ and two H+). The GI/1 and GII/4 VLPs bound extensively to duodenal and buccal tissues from either A+ or H+ pigs, but surprisingly, GII/1 and GII/3 VLPs bound minimally to the duodenum of an A+ pig. The VLP binding was partially inhibited by A-, H1-, or H2-specific monoclonal antibodies, but was completely blocked by porcine mucin. Comparing the A/H phenotypes of 65 HS66-inoculated Gn pigs from our previous study, we found that significantly more A+ and H+ pigs (51%) than non-A+ and non-H+ pigs (12.5%) shed virus. From the 22 convalescent pigs, significantly more A+ or H+ pigs (66%) than non-A+ or H+ pigs (25%) seroconverted.

scholarly journals NMR Experiments Shed New Light on Glycan Recognition by Human and Murine Norovirus Capsid Proteins

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 416
Author(s):  
Robert Creutznacher ◽  
Thorben Maass ◽  
Patrick Ogrissek ◽  
Georg Wallmann ◽  
Clara Feldmann ◽  
...  
Keyword(s):  
Blood Group ◽  
Protein Interactions ◽  
Capsid Proteins ◽  
Blood Group Antigens ◽  
Biological Processes ◽  
Murine Norovirus ◽  
Human Norovirus ◽  
Head Groups ◽  
Significant Difference

Glycan–protein interactions are highly specific yet transient, rendering glycans ideal recognition signals in a variety of biological processes. In human norovirus (HuNoV) infection, histo-blood group antigens (HBGAs) play an essential but poorly understood role. For murine norovirus infection (MNV), sialylated glycolipids or glycoproteins appear to be important. It has also been suggested that HuNoV capsid proteins bind to sialylated ganglioside head groups. Here, we study the binding of HBGAs and sialoglycans to HuNoV and MNV capsid proteins using NMR experiments. Surprisingly, the experiments show that none of the norovirus P-domains bind to sialoglycans. Notably, MNV P-domains do not bind to any of the glycans studied, and MNV-1 infection of cells deficient in surface sialoglycans shows no significant difference compared to cells expressing respective glycans. These findings redefine glycan recognition by noroviruses, challenging present models of infection.

Seasonal Tracking of Histo-Blood Group Antigen Expression and Norovirus Binding in Oyster Gastrointestinal Cells

2008 ◽  
Vol 71 (8) ◽  
pp. 1696-1700 ◽  
Author(s):  
PENG TIAN ◽  
ANNA L. ENGELBREKTSON ◽  
ROBERT E. MANDRELL
Keyword(s):  
Blood Group ◽  
Seasonal Pattern ◽  
Antigen Expression ◽  
Blood Group Antigen ◽  
Viral Gastroenteritis ◽  
Blood Group Antigens ◽  
Pacific Oysters ◽  
Crassostrea Sikamea ◽  
Highly Correlated ◽  
Viral Receptors

Noroviruses (NORs) are the most common cause of viral gastroenteritis outbreaks. Outbreaks are often associated with the consumption of contaminated oysters and generally occur between the months of November and March, when oysters produce the highest levels of glycogen. Oyster glycogen has been proposed as playing a role in NOR accumulation. Recent research indicates that histo-blood group antigens (HBGAs) function as viral receptors on human gastrointestinal cells. In this study, oyster glycogen was tested to determine whether it contains HBGA-like molecules and whether it plays a role in NOR binding. The correlation between the amount of HBGA expression and NOR binding also was measured. We also tested whether seasonal changes affected HBGA expression and binding of recombinant NORs. The results indicate that recombinant NOR binding is highly correlated with HBGA expression in Virginica (Crassostrea virginica), Pacific (Crassostrea gigas), and Kumamato (Crassostrea sikamea) oysters, but the association does not have a seasonal pattern. No obvious trend in either HBGA expression or recombinant NOR binding by month was noted. A significant increase in recombinant NOR binding was observed in Virginica and Pacific oysters in a season not generally associated with NOR gastroenteritis outbreaks. A significant increase in HBGA expression also was observed for Pacific and Virginica oysters in the same season. Paradoxically, HBGA expression and NOR binding both were higher in oysters produced in the non–NOR gastroenteritis season (April through October) than in those produced in the NOR gastroenteritis season (November through March), suggesting that seasonal NOR gastroenteritis outbreaks are not associated with high levels of HBGA expression or NOR binding.

Characterization of a Histo-Blood Group Antigen-like Substance in Romaine Lettuce That Contributes to Human Norovirus Attachment

2019 ◽  
Vol 68 (5) ◽  
pp. 1207-1212 ◽  
Author(s):  
Zilei Zhang ◽  
Danlei Liu ◽  
Qingping Wu ◽  
Yu Lu ◽  
Peng Tian ◽  
...  
Keyword(s):  
Blood Group ◽  
Blood Group Antigen ◽  
Romaine Lettuce ◽  
Human Norovirus

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 Structural Constraints on Human Norovirus Binding to Histo-Blood Group Antigens

mSphere ◽  
2016 ◽  
Vol 1 (2) ◽  
Author(s):  
Bishal K. Singh ◽  
Mila M. Leuthold ◽  
Grant S. Hansman
Keyword(s):  
Aspartic Acid ◽  
Blood Group ◽  
Blood Group Antigens ◽  
Structural Constraints ◽  
Human Norovirus ◽  
Genotype 4 ◽  
Human Noroviruses ◽  
X Ray ◽  
X Ray Crystallography ◽  
New Findings

ABSTRACT Human norovirus interacts with the polymorphic human histo-blood group antigens (HBGAs), and this interaction is thought to be important for infection. The genogroup II genotype 4 (GII.4) noroviruses are the dominant cluster, evolve every other year, and are thought to modify their binding interactions with different HBGA types. Most human noroviruses bind HBGAs, while some strains were found to have minimal or no HBGA interactions. Here, we explain some possible structural constraints for several noroviruses that were found to bind poorly to HBGAs by using X-ray crystallography. We showed that one aspartic acid was flexible or positioned away from the fucose moiety of the HBGAs and this likely hindered binding, although other fucose-interacting residues were perfectly oriented. Interestingly, a neighboring loop also appeared to influence the loop hosting the aspartic acid. These new findings might explain why some human noroviruses bound HBGAs poorly, although further studies are required.

scholarly journals Genetic Susceptibility to Human Norovirus Infection: An Update

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 226 ◽  
Author(s):  
Johan Nordgren ◽  
Lennart Svensson
Keyword(s):  
Genetic Susceptibility ◽  
Blood Group ◽  
Phenotypic Diversity ◽  
In Vivo Studies ◽  
Human Populations ◽  
Blood Group Antigens ◽  
Human Norovirus ◽  
The Impact ◽  
High Infectivity

Noroviruses are the most common etiological agent of acute gastroenteritis worldwide. Despite their high infectivity, a subpopulation of individuals is resistant to infection and disease. This susceptibility is norovirus genotype-dependent and is largely mediated by the presence or absence of human histo-blood group antigens (HBGAs) on gut epithelial surfaces. The synthesis of these HBGAs is mediated by fucosyl- and glycosyltransferases under the genetic control of the FUT2 (secretor), FUT3 (Lewis) and ABO(H) genes. The so-called non-secretors, having an inactivated FUT2 enzyme, do not express blood group antigens and are resistant to several norovirus genotypes, including the predominant GII.4. Significant genotypic and phenotypic diversity of HBGA expression exists between different human populations. Here, we review previous in vivo studies on genetic susceptibility to norovirus infection. These are discussed in relation to population susceptibility, vaccines, norovirus epidemiology and the impact on public health.

scholarly journals A phenome-wide association study of ABO blood groups

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Shun Li ◽  
C. M. Schooling
Keyword(s):  
Blood Pressure ◽  
Body Composition ◽  
Association Study ◽  
Blood Group ◽  
Density Lipoprotein ◽  
Blood Group Antigen ◽  
Abo Blood Group ◽  
Blood Group Antigens ◽  
Nucleotide Polymorphisms ◽  
Tag Snp

Abstract Background ABO blood group is associated with differences in lifespan, cardiovascular disease, and some cancers, for reasons which are incompletely understood. To gain sex-specific additional insight about potential mechanisms driving these common conditions for future interventions, we characterized associations of ABO blood group antigen across the phenotype sex-specifically. Methods We performed a phenome-wide association study (PheWAS) assessing the association of tag single nucleotide polymorphisms (SNPs) for ABO blood group antigens (O, B, A1, and A2) with 3873 phenotypes. Results The tag SNP for the O antigen was inversely associated with diseases of the circulatory system (particularly deep vein thrombosis (DVT)), total cholesterol, low-density lipoprotein cholesterol (LDL-C), and ovarian cancer, and positively associated with erythrocyte traits, leukocyte counts, diastolic blood pressure (DBP), and healthy body composition; the tag SNP for the A1 antigen tended to have associations in reverse to O. Stronger associations were more apparent for men than women for DVT, DBP, leukocyte traits, and some body composition traits, whereas larger effect sizes were found for women than men for some erythrocyte and lipid traits. Conclusion Blood group has a complex association with cardiovascular diseases and its major risk factors, including blood pressure and lipids, as well as with blood cell traits and body composition, with some differences by sex. Lower LDL-C may underlie some of the benefits of blood group O, but the complexity of associations with blood group antigen suggests overlooked drivers of common chronic diseases.

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