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.

Comparing Human Norovirus Surrogates: Murine Norovirus and Tulane Virus

2013 ◽  
Vol 76 (1) ◽  
pp. 139-143 ◽  
Author(s):  
KIRSTEN A. HIRNEISEN ◽  
KALMIA E. KNIEL
Keyword(s):  
Tap Water ◽  
Plaque Assay ◽  
Heat Treatments ◽  
Viral Infectivity ◽  
Murine Norovirus ◽  
Human Norovirus ◽  
Human Noroviruses ◽  
Ph Values ◽  
Significant Difference ◽  
Tulane Virus

Viral surrogates are widely used by researchers to predict human norovirus behavior. Murine norovirus (MNV) is currently accepted as the best surrogate and is assumed to mimic the survival and inactivation of human noroviruses. Recently, a new calicivirus, the Tulane virus (TV), was discovered, and its potential as a human norovirus surrogate is being explored. This study aimed to compare the behavior of the two potential surrogates under varying treatments of pH (2.0 to 10.0), chlorine (0.2 to 2,000 ppm), heat (50 to 75°C), and survival in tap water at room (20°C) and refrigeration (4°C) temperatures for up to 30 days. Viral infectivity was determined by the plaque assay for both MNV and TV. There was no significant difference between the inactivation of MNV and TV in all heat treatments, and for both MNV and TV survival in tap water at 20°C over 30 days. At 4°C, MNV remained infectious over 30 days at a titer of approximately 5 log PFU/ml, whereas TV titers decreased significantly by 5 days. MNV was more pH stable, as TV titers were reduced significantly at pH 2.0, 9.0, and 10.0, as compared with pH 7.0, whereas MNV titers were only significantly reduced at pH 10.0. After chlorine treatment, there was no significant difference in virus with the exception of at 2 ppm, where TV decreased significantly compared with MNV. Compared with TV, MNV is likely a better surrogate for human noroviruses, as MNV persisted over a wider range of pH values, at 2 ppm of chlorine, and without a loss of titer at 4°C.

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 Association between secretor status and Lewis phenotype with seronegative spondyloarthritis as indicator of autoimmunity

Genetika ◽  
2020 ◽  
Vol 52 (1) ◽  
pp. 127-136
Author(s):  
Ivan Busarcevic ◽  
Svetlana Vojvodic ◽  
Una Vojvodic
Keyword(s):  
Blood Group ◽  
Haemagglutination Inhibition ◽  
Gastrointestinal Symptoms ◽  
Blood Group Antigens ◽  
Control Subjects ◽  
Secretor Status ◽  
Lewis Blood Group ◽  
Increased Risk ◽  
Significant Difference ◽  
Seronegative Spondyloarthropathies

The classical paradigm of autoimmune pathogenesis involving specific genetic makeup and exposure to environmental triggers has been challenged recently by the addition of a third element, the loss of intestinal barrier function. Regardless of HLA B27 phenotype or gastrointestinal symptoms, evidence of ileitis, ileocolitis or colitis exists in patients with spondyloarthropathy. The FUT2 secretory gene is a strong candidate for Crohn's susceptibility by shaping the functional states of mucosal microbiota and may thus have influence on the release of zonulin, the main regulator of gut permeability. Gram negative bacteria precipitate and may be involved in the pathogenesis of spondyloarthropathies. Susceptibility to many infectious agents is associated with ABO blood group or secretor state. Patients who cannot secrete ABO and Lewis blood group antigens into body fluids, an ability controlled by a single gene on chromosome 19, are known to be at increased risk of certain autoimmune diseases associated with human leukocyte antigen (HLA) markers. Lewis (Le) blood group phenotype can be used to infer secretor status. The objective of this study was to determine the distribution of secretor state and Lewis blood group phenotype in patients with seronegative spondyloarthropathies and healthy control subjects. Hundred and ten (110) patients with seronegative spondyloarthropathies (58 females and 52 males) and 103 control (74 males and 29 females) subjects participated in this study. Samples of saliva and blood were subjected to haemagglutination inhibition tests for determination of secretor status and Lewis phenotype. A total of 92(84%) patients and 92 (89%) control subjects were secretors while 18 (16%) patients and 11 (11%) control subjects were non-secretors. There was no statistically significant difference (?2 1,461 p<0,05 and degrees of freedom 1) in distribution of secretor status in comparison to seronegative spondyloarthropathies by comparing two observed populations. Seven patients had modified (reduced) expression of Lewis b antigen on their erythrocytes. Reduction of Lewis b antigen expression was not observed on erythrocytes of healthy subjects. Reduced expression of Lewis b antigen could be a consequence of the inflammatory process within the gut and it also suggests several pathogenic mechanisms which may be relevant to the synthesis of Lewis antigens inside the gut or its absorption on erythrocytes in patients with spondyloarthropathy.

scholarly journals Changes of the expression of Lewis blood group antigens in glycoproteins of renal cancer tissues.

2013 ◽  
Vol 60 (2) ◽  
Author(s):  
Małgorzata Borzym-Kluczyk ◽  
Iwona Radziejewska
Keyword(s):  
Sialic Acid ◽  
Blood Group ◽  
Tumor Development ◽  
Renal Tissue ◽  
Cancer Tissue ◽  
Blood Group Antigens ◽  
Lewis Blood Group ◽  
Significant Difference ◽  
Cancer Tissues ◽  
Sialyl Lewisa

Sialic acid and sialyl Lewisa/x are found on N- and O-glycans of many human malignant cells. Carbohydrate antigens can be used as tumor markers, and an increase of their levels in cancer cells is associated with tumor progression. The aim of this study was to assess the level of some Lewis blood group antigens on glycoproteins in tumor (cancer tissue), intermediate zone (adjacent to tumor tissue), and normal renal cortex/medulla (uninvolved by tumor). The study was performed on tissues taken from 30 patients. Relative amounts of sugar structures of proteins with molecular masses above 30 kDa were determined by ELISA-like test with biotinylated lectins: MAA (Maackia amurensis), SNA (Sambucus nigra), and monoclonal antibodies anti-sialyl Lewisa/x.∙ Higher expression of all examined structures was revealed in cancer tissues. Significant increases were observed for sialic acid linked α 2-3 in cancer tissues when compared to healthy ones and also among intermediate and healthy tissues. The sialic acid linked α 2-6 and sialyl Lewisx structures were significantly increased in cancerous cells when compared to normal and intermediate renal tissue. In case of sialyl Lewisa antigen, a significant difference was discovered between normal and intermediate tissue. Our results confirm that the examined Lewis antigens can be involved in tumor development. Their increase in cancer tissues can suggest their specific role in the process.

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 Relationship of Blood Group Determinants on Helicobacter pylori Lipopolysaccharide with Host Lewis Phenotype and Inflammatory Response

2000 ◽  
Vol 68 (2) ◽  
pp. 937-941 ◽  
Author(s):  
Michael A. Heneghan ◽  
Ciaran F. McCarthy ◽  
Anthony P. Moran
Keyword(s):  
Helicobacter Pylori ◽  
Inflammatory Response ◽  
Blood Group ◽  
Chronic Gastritis ◽  
Bacterial Colonization ◽  
Neutrophil Infiltration ◽  
Blood Group Antigens ◽  
Significant Difference ◽  
H Pylori ◽  
Relationship Of

ABSTRACT As Lewis a (Lea) and Lewis b (Leb) blood group antigens are isoforms of Lewis x (Lex) and Lewis y (Ley) and are expressed in the gastric mucosa, we evaluated whether the patterns of expression of Lex and Ley on Helicobacter pylorilipopolysaccharides reflected those of host expression of Lea and Leb. When 79 patients (secretors and nonsecretors) were examined for concordance between bacterial and host Le expression, no association was found (χ2 = 5.734, 3 df, P = 0.125), nor was there a significant difference between the amount of Lex or Ley expressed on isolates from ulcer and chronic gastritis patients (P > 0.05). Also, the effect of host and bacterial expression of Le antigens on bacterial colonization and the observed inflammatory response was assessed. In ulcer patients, Lex expression was significantly related to neutrophil infiltration (r s = 0.481,P = 0.024), whereas in chronic gastritis patients significant relationships were found between Lexexpression and H. pylori colonization density (r s = 0.296, P = 0.03), neutrophil infiltrate (r s = 0.409,P = 0.001), and lymphocyte infiltrate (r s = 0.389, P = 0.002). Furthermore, bacterial Ley expression was related to neutrophil (r s = 0.271, P= 0.033) and lymphocyte (r s = 0.277,P = 0.029) infiltrates. Thus, although no evidence of concordance was found between bacterial and host expression of Le determinants, these antigens may be crucial for bacterial colonization, and the ensuing inflammatory response appears, at least in part, to be influenced by Le antigens.

scholarly journals Human Norovirus Interactions with Histo-Blood Group Antigens and Human Milk Oligosaccharides

2016 ◽  
Vol 90 (13) ◽  
pp. 5855-5859 ◽  
Author(s):  
Horst Schroten ◽  
Franz-Georg Hanisch ◽  
Grant S. Hansman
Keyword(s):  
Virus Infection ◽  
Human Milk ◽  
Blood Group ◽  
Blood Group Antigens ◽  
Human Milk Oligosaccharides ◽  
Binding Studies ◽  
Human Norovirus ◽  
Milk Oligosaccharides ◽  
Human Noroviruses ◽  
Binding Pockets

Human noroviruses interact with both human histo-blood group antigens (HBGAs) and human milk oligosaccharides (HMOs). The former are believed to be important for a virus infection, while the latter might act as natural decoys in the host during an infection. However, certain noroviruses are known to bind poorly to HBGAs and yet still cause infections; some interact with numerous HBGA types but are nonprevalent; and yet others bind HBGAs and seem to be increasing in prevalence. HBGAs and HMOs can be found as soluble antigens in humans, can be structurally alike, and can interact with equivalent residues at identical binding pockets on the capsid. In this Gem, we discuss HBGA and HMO binding studies for human noroviruses, concentrating on the clinically important genogroup II noroviruses. In short, the roles of HBGA and HMO interactions in norovirus infections are still unclear.

scholarly journals Salivary Secretor Status of Blood Group Antigens in Patients with Head and Neck Cancer

2019 ◽  
Vol 7 (3) ◽  
pp. 373-377
Author(s):  
Sedighe Bakhtiari ◽  
Soheila Mani Far ◽  
Zahra Alibakhshi ◽  
Mohammad Shirkhoda ◽  
Fahimeh Anbari
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Blood Group ◽  
Neck Cancer ◽  
Body Fluids ◽  
Head And Neck Cancers ◽  
Blood Type ◽  
Blood Group Antigens ◽  
Secretor Status ◽  
Significant Difference

BACKGROUND: Head and neck cancers include malignancies of the scalp and neck skin, nasal cavity, paranasal sinuses, oral cavity, salivary glands, pharynx and larynx. The term ABO secretor refers to people who secrete blood group antigens in their body fluids such as saliva, sweat, tears, semen, and serum. Non-secretors refer to those who do not secrete their blood group antigens in their body fluids. The lack of blood type antigens in body discharge increases the susceptibility to certain types of diseases and infection. AIM: Our study aimed to investigate the relationship between the secretion of blood groups in the saliva of patients with head and neck cancers. MATERIAL AND METHODS: This case-control study was performed on 110 people (57 patients with head and neck cancer who were referred to Imam Khomeini Hospital, Tehran and 53 cancer-free controls). Five ml of non-stimulated saliva were collected by the spitting method. By agglutination or lack of agglutination in the test tubes, we determined the patient’s secretor or non-secretor condition. RESULTS: In terms of secretor status, 52.7% of all samples were secretors. In the case group, 19 out of 57 cases (33.3%) were secretors, and 38 were non-secretors (66.7%). In the control group, 39 out of 53 cases (73.6%) were secretors, and 14 cases were non-secretors (26.4%). There was a significant difference in the percentage of non-secretors between the two groups (p = 0.00). CONCLUSION: People with non-secretor status may be more prone to develop head and neck cancer. The presence of these antigens in saliva may have a protective effect.

scholarly journals Norovirus Attachment and Entry

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 495 ◽  
Author(s):  
Vincent R. Graziano ◽  
Jin Wei ◽  
Craig B. Wilen
Keyword(s):  
Viral Entry ◽  
Molecular Mechanisms ◽  
Viral Gastroenteritis ◽  
Blood Group Antigens ◽  
Cell Tropism ◽  
Murine Norovirus ◽  
Human Norovirus ◽  
Future Directions ◽  
Minor Capsid Protein

Human norovirus is a major human pathogen causing the majority of cases of viral gastroenteritis globally. Viral entry is the first step of the viral life cycle and is a significant determinant of cell tropism, host range, immune interactions, and pathogenesis. Bile salts and histo-blood group antigens are key mediators of norovirus entry; however, the molecular mechanisms by which these molecules promote infection and the identity of a potential human norovirus receptor remain unknown. Recently, there have been several important advances in norovirus entry biology including the identification of CD300lf as the receptor for murine norovirus and of the role of the minor capsid protein VP2 in viral genome release. Here, we will review the current understanding about norovirus attachment and entry and highlight important future directions.

scholarly journals Secretor Status of ABO Antigens in Saliva of a Defined Group of Iranian Patients with Pemphigus Vulgaris: A Case-Control Study

Scientifica ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Sedigheh Bakhtiari ◽  
Zahra Yadegari ◽  
Marziyeh Kaviyani ◽  
Zahra Namazi ◽  
Mahin Bakhshi
Keyword(s):  
Blood Group ◽  
Case Control Study ◽  
Pemphigus Vulgaris ◽  
Case Control ◽  
Blood Type ◽  
Blood Group Antigens ◽  
Secretor Status ◽  
The People ◽  
Significant Difference ◽  
Control Study

Introduction. Pemphigus is a chronic inflammatory and autoimmune disease which can cause blisters and mucocutaneous erosions. ABO secretor refers to those who secrete ABO blood group antigens based on their blood type in body fluids such as saliva, sweat, tears, semen, and serum. Previous studies showed that nonsecretor people are more prone to certain autoimmune diseases. Aim. The aim of this study was to determine the ABO secretor status in the saliva of patients with pemphigus vulgaris. Materials and Methods. This case-control study was conducted on 35 patients with pemphigus vulgaris and 35 healthy controls. The two groups were matched for age and gender. Pemphigus vulgaris diagnosis was confirmed by histopathology and direct immunofluorescence microscopy. ABO blood grouping was done, and 5 ml of unstimulated saliva was collected to determine secretor status. Secretors were recognized from nonsecretors by the Wiener agglutination inhibition test. Results were extracted by using statistical chi-square and Fisher’s exact tests. Results. 16 male and 19 female patients aged 49.43 ± .12.37 years were compared with 16 male and 19 female controls aged 46.43 ± 11.88 years. The most frequent blood group among case and control groups was O (54.3% and 60%, respectively). There was no significant difference in blood groups (P=0.73). 90% of the samples were ABO secretors. The patient group included 31 (88.6%) and the control group included 32 (91.4%) ABO secretors; there was no significant difference between the two groups (P=1.000). Conclusion. In this study, we observed that the people with nonsecretor status in comparison with the people with secretor status are not more susceptible to develop pemphigus vulgaris.

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