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Journal of Virology, November 2008, p. 10756-10767, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00802-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Noroviruses Distinguish between Type 1 and Type 2 Histo-Blood Group Antigens for Binding{triangledown}

Haruko Shirato,1* Satoko Ogawa,1 Hiromi Ito,2 Takashi Sato,2 Akihiko Kameyama,2 Hisashi Narimatsu,2 Zheng Xiaofan,3 Tatsuo Miyamura,1 Takaji Wakita,1 Koji Ishii,1 and Naokazu Takeda1

Department of Virology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan,1 Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan,2 Blood Centre of Zhejiang Province, 345 Wulin Road, Hangzhou, Zhejiang Province 310006, China3

Received 15 April 2008/ Accepted 6 August 2008


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ABSTRACT
 
Norovirus (NoV) is a causative agent of acute gastroenteritis. NoV binds to histo-blood group antigens (HBGAs), namely, ABH antigens and Lewis (Le) antigens, in which type 1 and type 2 carbohydrate core structures constitute antigenically distinct variants. Norwalk virus, the prototype strain of norovirus, binds to the gastroduodenal junction, and this binding is correlated with the presence of H type 1 antigen but not with that of H type 2 antigen (S. Marionneau, N. Ruvoen, B. Le Moullac-Vaidye, M. Clement, A. Cailleau-Thomas, G. Ruiz-Palacois, P. Huang, X. Jiang, and J. Le Pendu, Gastroenterology 122:1967-1977, 2002). It has been unknown whether NoV distinguishes between the type 1 and type 2 chains of A and B antigens. In this study, we synthesized A type 1, A type 2, B type 1, and B type 2 pentasaccharides in vitro and examined the function of the core structures in the binding between NoV virus-like particles (VLPs) and HBGAs. The attachment of five genogroup I (GI) VLPs from 5 genotypes and 11 GII VLPs from 8 genotypes, GI/1, GI/2, GI/3, GI/4, GI/8, GII/1, GII/3, GII/4, GII/5, GII/6, GII/7, GII/12, and GII/14, to ABH and Le HBGAs was analyzed by enzyme-linked immunosorbent assay-based binding assays and Biacore analyses. GI/1, GI/2, GI/3, GI/4, GI/8, and GII/4 VLPs were more efficiently bound to A type 2 than A type 1, and GI/8 and GII/4 VLPs were more efficiently bound to B type 2 than B type 1, indicating that NoV VLPs distinguish between type 1 and type 2 carbohydrates. The dissociation of GII/4 VLPs from B type 1 was slower than that from B type 2 in the Biacore experiments; moreover, the binding to B type 1 was stronger than that to B type 2 in the ELISA experiments. These results indicated that the type 1 carbohydrates bind more tightly to NoV VLPs than the type 2 carbohydrates. This property may afford NoV tissue specificity. GII/4 is known to be a global epidemic genotype and binds to more HBGAs than other genotypes. This characteristic may be linked with the worldwide transmission of GII/4 strains. GI/2, GI/3, GI/4, GI/8, GII/4, and GII/7 VLPs bound to Lea expressed by nonsecretors, suggesting that NoV can infect individuals regardless of secretor phenotype. Overall, our results indicated that HBGAs are important factors in determining tissue specificity and the risk of transmission.


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INTRODUCTION
 
Norovirus (NoV), a member of the family Caliciviridae (1), is a major cause of water- and food-borne acute nonbacterial gastroenteritis and comprises many morphologically similar but antigenically diverse groups of viruses (8, 11, 22). Recent progress in genetic studies has enabled us to divide human NoV into at least three genogroups, genogroup I (GI), GII, and GIV, which contain at least 15, 18, and 1 genotype, respectively (20).

Histo-blood group antigens (HBGAs) are carbohydrates that contain structurally related saccharide moieties. H antigen (Fuc{alpha}1-2Gal), i.e., O-type antigen, is generated by a fucose transfer to a galactose residue with an {alpha}1-2 linkage. A antigen [GalNAc{alpha}1-3(Fuc{alpha}1-2)Gal] and B antigen [Gal{alpha}1-3(Fuc{alpha}1-2)Gal] of ABH HBGAs are generated by a transfer of GalNAc and Gal, respectively, to an H structure irrespective of the carbohydrate core structure. The core structures are classified into four major structures, type 1 (Galβ1-3GlcNAcβ), type 2 (Galβ1-4GlcNAcβ), type 3 (Galβ1-3GalNAc{alpha}), and type 4 (Galβ1-3GalNAcβ). The fucose transfer of ABH antigens in erythrocytes is catalyzed by FUT1, a member of the fucosyltransferase family, whereas it is catalyzed by a different fucosyltransferase, FUT2, in saliva and mucosal secretions (31). Individuals who have null FUT2 alleles cannot synthesize ABH antigens in secretions and are called nonsecretors, although ABH antigens can be expressed in erythrocytes via FUT1 (21). FUT2 alleles of Caucasian nonsecretors are completely inactivated by nonsense mutations, whereas those of Asian nonsecretors are incompletely inactivated by missense mutations (23, 41). Thus, Asian nonsecretors are incomplete nonsecretors and produce a small amount of ABH HBGAs in secretions. FUT2 is essential for the fucose transfer to the type 1 structure (Galβ1-3GlcNAc) required to generate the H type 1 structure (Fuc{alpha}1-2Galβ1-3GlcNAc), a precursor structure for Lewis b (Leb) [Fuc{alpha}1-2Galβ1-3(Fuc{alpha}1-4)GlcNAc], in secretions. The FUT3 enzyme is required for the fucose transfer to type 1 or H type 1 to generate Lewis a (Lea) [Galβ1-3(Fuc{alpha}1-4)GlcNAc] or Leb, respectively.

Virus-like particles (VLPs) derived from the prototype strain of NoV, Norwalk virus (NV/68), bind to HBGAs in saliva from secretor individuals. They preferentially bind to H type 1 and Leb synthetic carbohydrates (12, 14, 15, 24, 26). Although NV/68 VLPs bind to type A antigens in saliva and synthetic type A carbohydrates, they bind to neither type B synthetic carbohydrates nor the majority of type B antigens in saliva (12, 14, 15, 24). From previous volunteer challenge studies, there is strong evidence that this carbohydrate binding is essential for NV/68 infection (16, 24). Nonsecretors were not infected after the challenge with NV/68. Furthermore, type O secretors are more likely to be infected with NV/68; conversely, type B secretors are less likely to be infected with NV/68. However, other NoV VLPs display different ABH and Lewis carbohydrate-binding profiles (12-15): indeed, epidemiological studies have shown that some NoV strains could infect individuals with other ABH or secretor phenotypes (34).

Type 1 core structures are widely expressed in endodermally derived tissues, such as lining epithelia and glandular epithelia (32). On the other hand, type 2 core structures are found mainly in ecto- or mesodermally derived tissues, including skin and erythrocytes (7, 10, 32). In the human gastroduodenal junction, type 1 structures are found exclusively at the level of the surface epithelia whereas type 2 structures are preferentially found at the glandular level (27). Immunohistochemical analysis showed that the binding of recombinant NV/68 (rNV/68) to the gastroduodenal junction correlated with the presence of H type 1 antigen but not with that of H type 2 antigen (26). In a human GII/4 infection experiment, pigs that expressed either A or H antigen on the intestinal mucosa had significantly higher rates of diarrhea and seroconversion in response to the strain, and fecal shedding of virus was also significantly higher (5). Therefore, in pigs and in humans, the expression of HBGAs may lead to increased susceptibility to NoV infection. The rNV/68 VLP has been reported to bind synthetic H carbohydrates in the following order of strength: H type 1 trisaccharides, H type 2 trisaccharides, and H disaccharides (17). Meanwhile Harrington et al. reported that this strain had higher binding activity for H type 1 trisaccharides than for H type 3 trisaccharides (12). Although these reports suggest that rNV/68 VLP may recognize the linkages and components in the core structures of the HBGAs, this has not yet been proven. Moreover, it has not been known whether NoV VLPs distinguish between the type 1 and type 2 chains of A and B antigens.

To investigate the binding properties of NoV strains for HBGAs and to determine whether NoV distinguishes between type 1 and type 2 chains of HBGAs, the attachment of 5 GI VLPs from 5 genotypes and 11 GII VLPs from 8 genotypes to ABH and LeaLeb HBGAs was analyzed by enzyme-linked immunosorbent assay (ELISA)-based binding assays and Biacore analysis.


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MATERIALS AND METHODS
 
Recombinant VLPs. The recombinant VLPs used in this study are shown in Table 1 (11, 20a, 22a, 22b, 22c, 22d, 41a). VLPs were prepared by infecting subconfluent Tn5 insect cells with the recombinant baculoviruses as described previously (11). Briefly, the culture medium was harvested at 6 days after infection, centrifuged at 1,000 x g for 10 min to remove the cell debris, and further centrifuged at 10,000 x g for 30 min to remove the baculoviruses. The VLPs in the supernatant were concentrated by centrifugation at 100,000 x g for 2 h at 4°C in an SW28 rotor (Beckman Instruments, Inc., Palo Alto, CA). The pellet was resuspended in a solution containing CsCl (1.9 g/4.5 ml) and centrifuged at 120,000 x g for 20 h at 10°C in an SW50.1 rotor (Beckman). Peak fractions containing the VLPs were pooled, diluted with phosphate-buffered saline (PBS) (pH 7.5), and centrifuged at 200,000 x g for 2 h at 4°C in an SW50.1 rotor. The purified VLPs were examined by electron microscopy, and it was confirmed that the preparations form particles similar to native NoV and do not contain VP2 aggregates, as described previously (11). The VLPs were also examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein concentrations were determined using the Bio-Rad protein assay kit (Bio-Rad Laboratories, Hercules, CA) with bovine serum albumin as the protein standard. Tn5 cells, an insect cell line from Trichoplusia ni (Invitrogen, San Diego, CA), were grown at 27°C with Ex-CELL 400 medium (JRH Biosciences, Lenexa, KS). The phylogenetic analysis of the 16 NoV strains, which classified them into 13 clusters, was described previously (11).


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  		TABLE 1. Recombinant VLPs used in this study

Saliva samples and blood group antigens. Saliva samples were collected from 29 healthy Japanese donors: specifically, 13 (45%) males (average age, 41 years old; range, 29 to 59 years old) and 16 (55%) females (average age, 36 years old; range, 23 to 62 years old). The saliva samples were boiled for 10 min immediately after collection and centrifuged for 5 min at 13,000 x g. The clear supernatant was collected and stored at –30C° until use.

The samples were assayed for the presence of H, A, and B antigens by hemagglutination inhibition. Either 100 µl of anti-H lecithin (Gamma Biologicals, Inc., Houston, TX), 50 µl of anti-A antibody (Gamma Biologicals, Inc.), or anti-B antibody (Gamma Biologicals, Inc.) was mixed with an equal volume of each undiluted saliva sample and incubated for 10 or 20 min at 26°C. Then, 50 µl of a 3 to 4% suspension of indicator O (Gamma Biologicals, Inc.), A1 (Gamma Biologicals, Inc.), or B (Gamma Biologicals, Inc.) was added. The mixture was left at 26°C for 5 min and centrifuged at 125 x g for 1 min. The amount of HBGAs was measured in a semiquantitative manner using serially diluted saliva (40). Serial twofold dilutions of the samples were prepared (1- to 256-fold dilution) and assayed by hemagglutination inhibition assay as described above. Informed consent was obtained from all donors in 2003 before their participation according to ethical code 28 of the National Institute of Infectious Diseases, Japan.

Enzymatic preparation of monovalent carbohydrate-biotin reagents. For the preparation of the GlcNAcβ1-3Galβ1-biotin derivative, a reaction mixture containing 25 mM HEPES buffer (pH 7.0), 10 mM MnCl2, biotin-labeled galactose, an appropriate concentration of UDP-GlcNAc, and purified β1,3-N-acetylglucosaminyltransferase 2 (β3GnT2) (38) was used. Biotin-labeled galactose, UDP-GlcNAc, and β3GnT2 were the acceptor, donor substrate, and enzyme, respectively. The substrates and enzyme were added to a reaction mixture containing 25 mM HEPES buffer and 10 mM MnCl2 and incubated at 37°C for 36 h. The enzyme was removed with an Ultrafree-MC column (Millipore, Bedford, MA), and the product was purified using reversed-phase high-performance liquid chromatography. For the preparation of the galactosylated derivatives Galβ1- 3GlcNAcβ1-3Galβ1-biotin and Galβ1-4GlcNAcβ1-3Galβ1-biotin, a reaction mixture containing GlcNAcβ1-3Galβ1-biotin and UDP-Gal was used. β1,3-Galactosyltransferase-5 (18) and β1,4-galactosyltransferase-1 (28) were added to the solution to synthesize type 1 and type 2 structures, respectively. After incubation at 37°C for 20 h, the removal of the enzyme and the purification of the products were performed as described above. For the preparation of the fucosylated derivatives Fuc{alpha}1-2Galβ1-3GlcNAcβ1-3Galβ1-biotin and Fuc{alpha}1-2Galβ1-4GlcNAcβ1-3Galβ1-biotin (H types 1 and 2, respectively, in Fig. 1A), a reaction mixture containing GDP-Fuc, FUT2, and the galactosylated derivatives as the acceptor substrate was used. After incubation at 37°C for 24 h, the products were purified as described above. For the preparation of the derivatives with the A-antigen structure, GalNAc{alpha}1-3(Fuc{alpha}1-2)Galβ1-3GlcNAcβ1-3Galβ1- biotin and GalNAc{alpha}1-3(Fuc{alpha}1-2)Galβ1-4GlcNAcβ1-3Galβ1-biotin (A types 1 and 2, respectively, in Fig. 1A), a reaction mixture containing UDP-GalNAc, the A enzyme, and the fucosylated derivatives as the acceptor substrate was used. After incubation at 37°C for 15 h, the product was purified. For the preparation of derivatives with B-antigen structure, Gal{alpha}1-3(Fuc{alpha}1-2)Galβ1-3GlcNAcβ1-3Galβ1-biotin and Gal{alpha}1-3(Fuc{alpha}1-2)Galβ1-4GlcNAcβ1-3Galβ1-biotin (B types 1 and 2, respectively, in Fig. 1A), a reaction mixture containing UDP-Gal, the B enzyme, and the fucosylated derivatives as the acceptor substrate was used. After incubation at 37°C for 15 h, the products were purified. The monovalent carbohydrate-biotin reagents were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (Reflex IV; Bruker-Daltonik GmbH) as previously described (19).


Figure 1
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  		FIG. 1. Diagram of carbohydrate structures used in this study. Monovalent carbohydrate-biotin reagents (A) were synthesized and used in the experiments shown in Fig. 5 and 6, and multivalent carbohydrate-biotin reagents (B) were used in the experiments shown in Fig. 4. Glc, glucose; Fuc, fucose; Gal, galactose; GlcNAc, N-acetylglucosamine; Lac, lactose; GalNAc, N-acetylgalactosamine; R1, biotin; R2, polyacrylamide with biotin.

ELISA-based binding assay. Two ELISA-based assays were used to detect and quantify NoV VLP attachment to HBGAs. In the first assay, a 96-well microplate (Thermo Labsystems, Franklin, MA) was coated with 100 µl of serially twofold-diluted saliva with coating buffer (50 mM carbonate-bicarbonate buffer, pH 9.6) (Sigma, St. Louis, MO) and incubated overnight at 37°C in a wet atmosphere. The wells were washed three times with 300 µl of PBS containing 0.05% Tween 20 (PBS-T) and then blocked with 200 µl of PBS containing 5% skim milk (SM/PBS) for 1 h at room temperature. After the well was washed three times with PBS-T, the VLPs (1 µg/ml) in 100 µl of 1% SM/PBS-T were added and incubated for 1 h at 37°C. The coating buffer was used for the negative control. The plates were washed six times with PBS-T, and 100 µl of the rabbit anti-recombinant NoV VLP antiserum (1:2,000) in 1% SM/PBS-T was added and incubated for 1 h at 37°C. After the well was washed six times with PBS-T, 100 µl of horseradish peroxidase-conjugated anti-rabbit immunoglobulin G (Zymed Laboratories Inc., San Francisco, CA) in 1% SM/PBS-T was added and incubated for 1 h at 37°C. The plates were washed six times with PBS-T, 100 µl of O-phenylenediamine (Sigma) was added as a substrate, and incubation proceeded at room temperature. After 30 min, 50 µl of 4 N H2SO4 was added to stop the reaction and the optical density at 492 nm was measured. A convalescent-phase serum from a patient infected with the GI/2 258 strain and r258 were used for the internal standard.

In the second assay, multivalent carbohydrate-biotin reagents conjugated to polyacrylamide (CHO-PAA-biotin; Glycotech, Rockville, MD) (Fig. 1B) were rehydrated to 1 mg/ml with 0.3 M sodium phosphate buffer and diluted to 2.5 µg/ml with Tris-buffered saline. The carbohydrates (100 µl per well) were added to streptavidin-precoated plates (Thermo Electron Corporation, Vantaa, Finland) and incubated for 2 h at 37°C. The plates were then blocked with 300 µl of 5% SM/PBS overnight at 4°C. VLPs (1 µg/ml) in a 100-µl volume of 5% SM/PBS were added and incubated for 4 h at 37°C. The plates were washed six times with PBS-T, and 100 µl of the rabbit anti-recombinant NoV VLP antiserum (1:2,000) in 5% SM/PBS was added and incubated for 2 h at 37°C. After the well was washed six times with PBS-T, 100 µl of horseradish peroxidase-conjugated anti-rabbit immunoglobulin G in 5% SM/PBS was added and incubated for 1 h at 37°C. The plates were washed six times with PBS-T, and binding was detected using O-phenylenediamine. To measure dose-dependent binding of VLPs to the monovalent carbohydrate-biotin reagents (Fig. 1B), the reagents were rehydrated with 0.3 M sodium phosphate buffer and diluted to 1 pmol/µl with Tris-buffered saline. Serial twofold dilutions of the regents were prepared (1.0 to 0.016 pmol/µl) and used to coat streptavidin-precoated plates. The binding of the VLPs was detected by polyclonal rabbit anti-VLPs.

SPR assay. The interaction between the VLPs and monovalent carbohydrate-biotin reagents (Fig. 1A) was examined by surface plasmon resonance (SPR) assay at 25°C with a Biacore 2000 instrument. The running buffer used in this assay was 20 mM Tris-HCl, pH 7.4, 150 mM NaCl, 2 mM MgCl2, and 2 mM CaCl2 containing 0.005% p20. A research-grade streptavidin-coated sensor chip (Biacore AB, Uppsala, Sweden) was pretreated with three injections of 1 M NaCl-50 mM NaOH at the flow rate of 5 µl/min/injection. The monovalent carbohydrate-biotin reagents (Fig. 1A) were rehydrated to 1 mg/ml with 0.3 M sodium phosphate buffer and diluted to 10-fmol/µl with the same buffer. The biotinylated oligosaccharides were captured on the chip. A 10-fmol/µl solution of each biotinylated oligosaccharide was then injected at 5 µl/min until an amount corresponding to 80 resonance units (RU) for H type 1 and H type 2 or 100 RU for A type 1, A type 2, B type 1, and B type 2 was captured on each independent surface of the sensor chip. A signal of 100 RU corresponds approximately to a surface concentration change of 0.1 ng/mm2. The carbohydrate-free surface of a sensor chip was used as a negative control. The VLPs (100 µg/ml) in the running buffer were injected at a flow rate of 20 µl/min for 120 s over all surfaces of the sensor chip to monitor the associations between VLPs and oligosaccharides. After injection, the VLPs were replaced with the running buffer to monitor their dissociations.


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RESULTS
 
Saliva phenotypes. HBGAs and secretor status are known to be associated with susceptibility to NoV infection, and these characteristics are represented in saliva (9). To determine the phenotypes of saliva samples, a hemagglutination inhibition assay was performed as described in Materials and Methods. According to the presence or absence of H, A, and B antigens, the 29 saliva samples were divided into 5 groups (Table 2), in which 1 specimen, no. 26, had an unexpected phenotype, H negative and A positive (Table 2). Therefore, this phenotype was further examined by an ELISA-based binding assay using r124, a VLP derived from a GI/1 strain which has 98% amino acid identity with the prototype Norwalk virus (NV/68) in the P2 domain. Two amino acid differences, at residues 370 and 376, are known not to be related to HBGA binding (3, 4, 42). The abilities of recombinant NV/68 to bind to H and A antigens have been well documented (12, 14-16, 24, 26). GII/1 rHV was used as a negative control for the binding assay (12). As depicted in Fig. 2, the binding of r124 occurred in a dose-dependent manner and high optical density values were observed up to 1:6,400 saliva dilutions (Fig. 2A, B, and D). The binding of r124 to the saliva containing B antigens was low, probably due to the inefficient binding ability of the terminal galactose of the type B epitope, as described previously (Fig. 2C) (12, 14, 15, 24). Although the saliva included A antigens and they were recognized by NV/68, the binding of r124 to the saliva from donor no. 26 was weak (Fig. 2E). In addition, four saliva samples containing H and A antigens had weak binding ability (Fig. 2A, no. 25 and 27 to 29). None of the saliva bound to rHV, as described previously (Fig. 2F) (12, 15).


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  		TABLE 2. Detection of soluble ABH antigens in saliva by hemagglutination inhibition assay


Figure 2
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  		FIG. 2. Dose-dependent binding of GI/1 r124 (A to E) or GII/1 rHV (F) to saliva. Serially twofold-diluted saliva samples, at 50- to 102,400-fold dilution, were used to coat the microplates. Convalescent-phase serum from a patient infected with the GI/2 258 strain and r258 were used for the internal standard. Coating buffer was used for the blank. The binding of the VLPs was detected by using polyclonal rabbit anti-VLPs as described in Materials and Methods.

Identification of incomplete nonsecretors. To further characterize these low binding abilities, the amounts of HBGAs in saliva samples were measured by semiquantitative hemagglutination inhibition assay. The phenotypes according to the amounts of HBGAs are summarized in Table 3. The saliva was grouped into five categories, characterized by A, AB, B, and O secretor status and nonsecretor status. These results were consistent with the results shown in Table 2. The phenotype of secretors was characterized by high secretion of H, A, or B antigens in saliva, as observed for donors 1 to 24. Each group of secretors was characterized by antigen content: H and A antigens for phenotype A; H, A, and B antigens for the AB phenotype; H and B antigens for phenotype B; and H antigen for phenotype O. The phenotype of the nonsecretors was characterized by low secretion of ABH antigens in saliva as observed for donors 25 to 29. These nonsecretors differ from those observed in Europe, because Japanese nonsecretors secrete a small amount of either H, A, or B antigen or both (23, 41). Therefore, they are described as incomplete nonsecretors. Measurement of the HBGAs enabled us to clarify the phenotypic difference between donors 1 to 5 and donors 25 and 27 to 29.


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  		TABLE 3. Semiquantitation of soluble ABH

Binding of GI NoV VLPs to HBGAs. The binding between GI VLPs and saliva was analyzed by using an ELISA-based binding assay. The saliva dilution of 1:1,600 was used because the strength of the binding to r124 was observed clearly at this dilution (Fig. 2). GI/1 r124 bound more efficiently to saliva from type O, A, and AB secretors than to that from type B secretors and incomplete nonsecretors (Fig. 3A), indicating that GI/1 r124 recognizes the H and A antigens. These results were consistent with the observation shown in Fig. 2. Three GI VLPs, GI/2 r258, GI/3 r645, and GI/4 rCV, had the same binding profiles and high binding activities for type O, A, and AB secretors and incomplete nonsecretors (Fig. 3B, C, and D). These results indicated that these three GI strains recognize the Lea antigen as well as the H and A antigens, because the saliva of the nonsecretors is characterized by high secretion of Lea antigen in saliva (40). GI/8 rW18 bound efficiently to all saliva samples regardless of secretor phenotype or blood type, indicating that GI/8 rW18 recognized the H, A, B, and Lea antigens (Fig. 3E). To further examine which HBGAs are involved in GI NoV attachment, a carbohydrate-VLP binding assay was performed with seven multivalent carbohydrate- biotin reagents: H type 1, H type 2, H type 3, tri-A, tri-B, Lea, and Leb. Basically, no discrepancy was found between the carbohydrate- and saliva-VLP binding assays, although the sensitivity of the former was higher than that of the latter (Fig. 4A to E; Table 4). Moreover, the following observations were obtained from the carbohydrate-VLP binding assay: (i) the results provide direct evidence that GI/2, GI/3, GI/4, and GI/8 VLPs recognized the Lea carbohydrate (Fig. 4B, C, D, and E); (ii) GI/1 and GI/2 VLPs bound to H type 3 (Fig. 4A and B); and (iii) GI/1, GI/4, and GI/8 VLPs recognized the Leb carbohydrate (Fig. 4D and E). We concluded that the binding properties of GI NoV VLPs for HBGAs were variable. However, four of five genotypes, GI/2, GI/3, GI/4, and GI/8, had high abilities to bind to the Lea antigen. This was a unique characteristic of GI which was not seen with GII, as mentioned below.


Figure 3
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  		FIG. 3. Binding between VLPs and saliva samples. The saliva samples were tested at a dilution of 1:1,600. The binding of the VLPs was detected by polyclonal rabbit anti-VLPs as described in Materials and Methods. The experiments were performed in triplicate and reproduced at least twice. Each data point represents the mean value (with error bar).


Figure 4
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  		FIG. 4. Binding between VLPs and synthetic histo-blood group carbohydrates. The multivalent carbohydrate-biotin reagents conjugated to polyacrylamide were tested at a concentration of 2.5 µg/ml. H type 1 trisaccharides and r124 were used for the internal standard. Tris-buffered saline was used for the blank. The binding of the VLPs was detected by polyclonal rabbit anti-VLPs as described in Materials and Methods. The experiments were performed in duplicate and reproduced at least twice. Each data point represents the mean value (with error bar).


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  		TABLE 4. HBGA recognition predicted by carbohydrate- and saliva-VLP binding assay

Binding of GII NoV VLPs to HBGAs. Similarly, a binding assay was performed with 11 GII VLPs. Two GII/1 VLPs (rHV and r485) and one GII/14 VLP (r47) did not bind to any of the saliva samples (Fig. 3F, G, and P), indicating that these three GII strains did not recognize the HBGAs in saliva. Two GII/3 VLPs (r18-3 and r336) and one GII/5 VLP (r754) bound to saliva samples from type A, AB, and B secretors, whereas they bound neither to type O secretors nor to incomplete nonsecretors (Fig. 3H, I, and K). The results indicate that these strains recognized the A and B antigens. GII/4 r104 and GII/7 r10-25 bound to all saliva samples (Fig. 3J and N), indicating that these two GII strains recognized the H, A, B, and Lea antigens. Two GII/6 VLPs, r7K and r445, had high binding ability for all blood-type secretors (Fig. 3L and M), indicating that these GII/6 strains recognize the H, A, or B antigen. GII/12 r76 bound to saliva from type AB and B secretors, although the binding levels were extremely low (Fig. 3O), indicating that r76 attached weakly to the B antigen. The saliva-VLP binding assay clearly showed that the strains of the same genetic clusters, rHV and r485 in GII/1, r18-3 and 336 in GII/3, and r7K and r445 in GII/6, have the same carbohydrate-binding patterns. To address which HBGAs are involved in the GII NoV attachment, a carbohydrate-VLP binding assay was performed as described above. The sensitivity was higher in the saliva- than the carbohydrate-VLP binding assay, and no discrepancy was found between the two binding assays, as was also the case with the GI assays (Fig. 4F to P and Table 4). Five other observations from the carbohydrate-VLP binding assay were made: (i) GII/3, GII/4, GII/6, and GII/7 VLPs bound to H type 3 (Fig. 4J, L, M, and N); (ii) GII/7 VLPs recognized the Lea carbohydrate (Fig. 4N); (iii) r104 hardly recognized the Lea carbohydrate (Fig. 4J), although the strain bound to incomplete nonsecretors strongly (Fig. 3J); (iv) r7K had binding activities for the Lea carbohydrate (Fig. 4L) (it had been hard to predict the r7K binding to the Lea antigen based on the saliva-VLP binding assay due to low binding activity for incomplete nonsecretors [Fig. 3L]); and (v) GII/4, GII/6, and GII/7 VLPs recognized the Leb carbohydrate (Fig. 4J, L, and N). We concluded that the binding properties of GII NoV VLPs for HBGAs were variable. However, there was no strain which strongly bound to the Lea antigen, although the strains of GII/6 and GII/7 had weak binding abilities for this antigen.

Both {alpha}1,2-fucosyl residue and carbohydrate core structures are needed for binding to HBGAs. To investigate the effect of the terminal saccharide residue(s), the binding activities between VLPs and synthetic type 1, 2, and 3 carbohydrates and synthetic H disaccharides that do not include the core structures were examined. As depicted in Fig. 4, none of the VLPs bound to synthetic type 1, 2, and 3 disaccharides, although GI/1, GI/2, GI/3, GII/3, GII/4, GII/6, and GII/7 VLPs had binding activities for H type 1, 2, or 3 (Fig. 4A to C, H to J, and L to N). These results suggested that the terminal {alpha}1,2-fucosyl residue on those H trisaccharides is one of the determinants responsible for the NoV binding. Moreover, NoV VLPs recognized the components in the core structures, because (i) seven VLP genotypes, including GI/2, GI/3, GII/3, GII/6, and GII/7 VLPs, unequally bound H type 1, 2, and 3 trisaccharides (Fig. 4B, C, H, I, and L to N); (ii) the binding abilities of those VLPs for H disaccharides were undetectable (Fig. 4B, C, H, I, and L to N); and (iii) the binding abilities of GI/1 r124 and GII/4 r104 for H disaccharides were lower than those for the H type 1, 2, and 3 trisaccharides (Fig. 4A and J). Next, we addressed whether the VLPs bound to synthetic A and B disaccharides that lack the {alpha}1,2-fucosyl residue. As shown in Fig. 4A to E, J, K, L, and N, those strains did not bind to the synthetic A and B disaccharides, with the exception of GI/2 r258. Therefore, besides the r258 strain, the {alpha}1,2-fucosyl residue is one of the determinants responsible for NoV binding, not only to H antigens but also to A and B antigens. We concluded that both the {alpha}1,2-fucosyl residue and core structures are needed for the binding of VLPs to the HBGAs.

NoV VLPs distinguish between type 1 and type 2 carbohydrates. Six monovalent carbohydrate-biotin reagents, H type 1, H type 2, A type 1, A type 2, B type 1, and B type 2 (Fig. 1A), were used in SPR Biacore experiments to determine whether NoV VLPs distinguish between type 1 and type 2 chains. These oligosaccharides were prepared using human recombinant glycosyltransferases. Unlike the organic synthesis of oligosaccharides, the reaction using glycosyltransferases is quite clear and efficient, and the monovalent carbohydrate-biotin reagents were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (Reflex IV; Bruker-Daltonik GmbH) (data not shown). Six strains, including GI/1, GI/2, GI/3, GI/4, GI/8, and GII/4 strains, bound to the monovalent carbohydrate-biotin reagents (Fig. 5), whereas 10 strains, including GII/1, GII/3, GII/4, GII/5, GII/6, GII/7, GII/12, and GII/14 strains, did not (data not shown). Basically, no discrepancy was found between the results of the ELISA-based binding assay with multivalent biotinylated reagents and those of the SPR Biacore experiments with monovalent biotinylated reagents, although the sensitivity of the former was higher than that of the latter (Fig. 4 and 5). GI/1, GI/2, GI/3, and GI/4 VLPs bound to A, but not to B, carbohydrates in the Biacore experiments, whereas GI/8 and GII/4 VLPs bound to both A and B carbohydrates. These results were consistent with the observation shown with the ELISA-based binding assay. Moreover, the following three observations were obtained from the Biacore experiments: (i) GI/3 and GII/4 VLPs were more efficiently bound to H type 2 than to H type 1 tetrasaccharides (Fig. 5C and F); (ii) five GI VLPs and r104 were more efficiently bound to A type 2 than to A type 1 pentasaccharides (Fig. 5G to L); and (iii) GI/8 and GII/4 VLPs were more efficiently bound to B type 2 than to B type 1 pentasaccharides (Fig. 5Q and R). These results indicate that NoV VLPs are able to distinguish between type 1 and type 2 carbohydrates. Moreover, type 1 carbohydrates are likely to bind more tightly to NoV VLPs than do the type 2 carbohydrates, because the dissociation of GII/4 r104 was slower in B type 1 than B type 2 (Fig. 5R). To further characterize this strong binding ability of type 1 carbohydrates, the binding between r104 and the six monovalent carbohydrate-biotin reagents was examined using an ELISA-based binding assay. The bindings of GII/4 VLPs were stronger in B type 1 pentasaccharides than in B type 2 pentasaccharides (Fig. 6). The Biacore assay allowed us to visualize each binding step in the 120-s reaction time, whereas ELISA allowed us to visualize only the last step in a total reaction time of about 7.5 h. Therefore, these results indicated that NoV VLPs bind more tightly to type 1 carbohydrates than to type 2 carbohydrates.


Figure 5
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  		FIG. 5. Interaction between NoV and synthetic histo-blood group carbohydrates. The monovalent carbohydrate-biotin reagents were captured on a streptavidin-coated sensor chip as described in Materials and Methods. Sensorgrams show the binding of the VLPs to immobilized carbohydrates, H type 1 and type 2 (A to F), A type 1 and type 2 (G to L), or B type 1 and type 2 (M to R). At 180 s, 40 µ1 of the VLP was injected at a flow rate of 20 µl/min and was replaced by the running buffer at 300 s. The binding curves of 180 to 300 s showed the association, whereas those of 300 to 500 s showed the dissociation. The binding curves between VLPs and two different carbohydrates were compared by overlaying the sensorgrams obtained on each surface. The experiments were reproduced at least twice. The y axis indicates the resonance signal as shown in resonance units (RU).


Figure 6
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  		FIG. 6. Dose-dependent binding of GII/4 r104 to the monovalent carbohydrate-biotin reagents. Serially twofold-diluted carbohydrate-biotin reagents, at 1.0 to 0.016 pmol/µl, were used to coat streptavidin-precoated plates. Tris-buffered saline was used for the blank. The binding of the VLPs was detected by polyclonal rabbit anti-VLPs as described in Materials and Methods. The optical densities at 492 nm are plotted against the dilutions.


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DISCUSSION
 
To date, the interaction between carbohydrates and 16 NoV VLPs, including 5 GI and 11 GII VLPs, has been described, with the conclusion that the carbohydrate-binding properties of NoV VLPs vary (12-15, 39). Our experiments with 16 VLPs from 5 GI genotypes and 8 GII genotypes have confirmed and extended these findings: not only the outmost sugar residues but also the type 1 and 2 core structures are important for VLP recognition.

In this study, we investigated the function of the core structures in the binding between NoV and H/A/B antigens. The GI/1, GI/2, GI/3, GI/4, GI/8, GII/3, GII/4, GII/6, and GII/7 VLPs were able to distinguish between type 1 and type 2 carbohydrates (Fig. 4 and 5). Moreover, the type 1 carbohydrates bound more tightly to NoV VLPs than did the type 2 carbohydrates, as indicated in the following results: (i) the dissociation of GII/4 VLPs from B type 1 pentasaccharides was slower than that from B type 2 pentasaccharides in the Biacore experiments (Fig. 5), and (ii) the binding of GII/4 VLPs to B type 1 pentasaccharides was stronger than that to B type 2 pentasaccharides in the ELISA experiments (Fig. 6). Avian and equine influenza viruses are known to preferentially bind to the terminal sialic acid {alpha}2-3Gal (SA{alpha}2-3Gal) linkage, while human influenza viruses preferentially bind to the SA{alpha}2-6Gal linkage (6, 35, 36), affording a major impact on the host specificity in the infection of influenza viruses. A similar relationship may exist between NoV carbohydrate recognition and its tissue specificity, because the binding of rNV/68 to the gastroduodenal junction has been reported to correlate with the presence of the H type 1 antigen but not that of the H type 2 antigen (26).

The importance of the terminal {alpha}1,2-fucosyl residue in the binding between NoV and H/A/B antigens has been analyzed in detail with the GI/1 NV/68 and GII/4 VA387 strains (3, 12, 26). In this study, we confirmed these findings with GI/1 and GII/4 strains. Moreover, we revealed that other genotypes which bind to H, A, and/or B antigen also require the {alpha}1,2-fucosyl residue for the binding. Although the GI/1, GI/2, GI/3, GII/3, GII/4, GII/6, and GII/7 VLPs bound to H type 1, type 2, and/or type 3 carbohydrates (Fig. 4A to C, H to J, and L to N), none of these VLPs bound to type 1, type 2, and type 3 carbohydrates (Fig. 4A to C, H to J, and L to N), suggesting that the terminal {alpha}1,2-fucosyl residue on those H trisaccharides may be the determinant responsible for the binding between NoV and the H antigen. Moreover, as shown in Fig. 4A to E, J to L, and N, GI/1, GI/2, GI/3, GI/4, GI/8, GII/4, GII/5, GII/6, and GII/7 VLPs, which bound to A and/or B trisaccharides, did not bind to A and B disaccharides, with the exception of GI/2 VLPs. Therefore, besides the GI/2 strain, the {alpha}1,2-fucosyl residue is the determinant for NoV binding not only to H antigens but also to A and B antigens. We had predicted that NoV would require additional terminal sugars, such as {alpha}1,2-fucose, for HBGA recognition. Unexpectedly, however, we found that GI/2 r258 recognized synthetic A disaccharide, which does not include fucose (Fig. 4B). Therefore, both core structures and additional terminal sugars may contribute to the virus-carbohydrate interaction.

In a previous work, the strain specificities of NoV-HBGA binding were reported (15). Those authors concluded that NoV-HBGA binding patterns could be classified into two groups, an A/B-binding group and a Lewis-binding group, and that there was no correlation between the binding patterns and the genogroup. Our results were consistent with their results when GI/1, GI/2, GII/1, GII/4, and GII/5 VLPs were used. However, GI/3 and GII/3 VLPs gave different results. This may be due to the difference in the amino acid residues at the putative carbohydrate-binding sites. The amino acid residues 267N, 291R, 292G, 293D, 300N, 322D, 327D, 328W, 329H, 331N, 333T, 334Q, 335F, 339S, 341T, 364I, 368N, 373L, 374S, 375W, 377S, and 430A (NV/68 numbering) on the P2 domain were predicted to be important for HBGA binding (3, 4, 42). There were no differences in residues between our GI/1, GI/2, GII/1, GII/4, and GII/5 strains and their corresponding strains, whereas some different residues were found in the GI/3 and GII/3 strains. The finding that a single amino acid change in the P domain resulted in a change in the pattern of HBGA binding (42) could explain the inconsistency of the results.

Differences in the reactivities between saliva samples and synthetic carbohydrates may be due to structural differences between the synthetic products and authentic antigens, which are thought to be present on mucin or mucin-like molecules (15, 39). In our experiment, the sensitivity of the saliva-VLP binding assay was better than that of the carbohydrate-VLP binding assay. On the other hand, the carbohydrate-VLP binding assay demonstrated H type 3, Lea, and Leb antigen recognition by NoV, which could not be detected with the saliva-VLP binding assay. This is why we have performed the binding assay with two ELISA methods.

In Biacore assays, we used 11 GII strains; however, only one strain (GII/4 genotype) revealed binding (Fig. 5). The remaining 10 GII strains did not bind to either A or B pentasaccharides (Fig. 5). GII/4 VLPs may recognize complicated carbohydrate structures as the authentic antigens and pentasaccharides, as shown in Fig. 3 and 5, whereas the remaining 10 GII viruses may only recognize simple structures, as shown in Fig. 4.

In conclusion, it is obvious that HBGAs are important factors in determining tissue specificity, although it is still unclear whether the HBGAs function as the primary receptor or enhance NoV infectivity and/or attachment to a common cellular receptor. GII/4 is known to be a global epidemic genotype (25, 29, 30) and to bind more HBGAs than other strains (15) (confirmed in this study). This characteristic may be linked with the worldwide transmission of GII/4 strains. Lewis HBGAs are also carbohydrate antigens expressed in the epithelial cells of gastrointestinal tracts (2, 33, 37). Interestingly, some strains of GI and GII bound to Lea expressed by nonsecretors. This means that NoV can infect individuals regardless of secretor phenotype. We are going to synthesize various Lewis-type glycans to further characterize NoV-Lewis HBGA binding abilities. In this study, the linkages and carbohydrate core structures appeared to be important in NoV-carbohydrate interaction. Since NoV forms many antigenically diverse groups, identification of the common NoV binding epitopes on host cells, if any, should be useful for the development of possible antiviral agents.


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ACKNOWLEDGMENTS
 
We thank Katsuo Natori, Tsutomu Kageyama (National Institute of Infectious Diseases, Tokyo, Japan), and Kunio Kamata (Denka-Seiken Co., Niigata, Japan) for their valuable assistance.

This work was supported in part by a grant for Research on Food Safety from the Ministry of Health, Labor and Welfare of Japan and by the R&D Project of the Industrial Science and Technology Frontier Program, supported by the New Energy and Industrial Technology Development Organization.


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FOOTNOTES
 
* Corresponding author. Mailing address: Department of Virology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-murayama, Tokyo 208-0011, Japan. Phone: (81)-42-561-0771. Fax: (81)-42-561-4729. E-mail: harukos{at}nih.go.jp Back

{triangledown} Published ahead of print on 13 August 2008. Back


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REFERENCES
 
    1
  1. Atmar, R. L., and M. K. Estes. 2001. Diagnosis of noncultivatable gastroenteritis viruses, the human caliciviruses. Clin. Microbiol. Rev. 14:15-37.[Abstract/Free Full Text]
    2. 2
  2. Bjork, S., M. E. Breimer, G. C. Hansson, K. A. Karlsson, and H. Leffler. 1987. Structures of blood group glycosphingolipids of human small intestine. A relation between the expression of fucolipids of epithelial cells and the ABO, Le and Se phenotype of the donor. J. Biol. Chem. 262:6758-6765.[Abstract/Free Full Text]
    3. 3
  3. Cao, S., Z. Lou, M. Tan, Y. Chen, Y. Liu, Z. Zhang, X. C. Zhang, X. Jiang, X. Li, and Z. Rao. 2007. Structural basis for the recognition of blood group trisaccharides by norovirus. J. Virol. 81:5949-5957.[Abstract/Free Full Text]
    4. 4
  4. Chakravarty, S., A. M. Hutson, M. K. Estes, and B. V. Prasad. 2005. Evolutionary trace residues in noroviruses: importance in receptor binding, antigenicity, virion assembly, and strain diversity. J. Virol. 79:554-568.[Abstract/Free Full Text]
    5. 5
  5. Cheetham, S., M. Souza, R. McGregor, T. Meulia, Q. Wang, and L. J. Saif. 2007. 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. J. Virol. 81:3535-3544.[Abstract/Free Full Text]
    6. 6
  6. Connor, R. J., Y. Kawaoka, R. G. Webster, and J. C. Paulson. 1994. Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology 205:17-23.[CrossRef][Medline]
    7. 7
  7. Dabelsteen, E., P. Vedtofte, S. I. Hakomori, and W. W. Young. 1982. Carbohydrate chains specific for blood group antigens in differentiation of human oral epithelium. J. Investig. Dermatol. 79:3-7.[CrossRef][Medline]
    8. 8
  8. Estes, M. K., J. M. Ball, S. E. Crawford, C. O'Neal, A. A. Opekun, D. Y. Graham, and M. E. Conner. 1997. Virus-like particle vaccines for mucosal immunization. Adv. Exp. Med. Biol. 412:387-395.[Medline]
    9. 9
  9. Grubb, R. 1948. Correlation between Lewis blood group and secretor character in man. Nature 162:933.
    10. 10
  10. Hakomori, S. 1981. Blood group ABH and Ii antigens of human erythrocytes: chemistry, polymorphism, and their developmental change. Semin. Hematol. 18:39-62.[Medline]
    11. 11
  11. Hansman, G. S., K. Natori, H. Shirato-Horikoshi, S. Ogawa, T. Oka, K. Katayama, T. Tanaka, T. Miyoshi, K. Sakae, S. Kobayashi, M. Shinohara, K. Uchida, N. Sakurai, K. Shinozaki, M. Okada, Y. Seto, K. Kamata, N. Nagata, K. Tanaka, T. Miyamura, and N. Takeda. 2006. Genetic and antigenic diversity among noroviruses. J. Gen. Virol. 87:909-919.[Abstract/Free Full Text]
    12. 12
  12. Harrington, P. R., L. Lindesmith, B. Yount, C. L. Moe, and R. S. Baric. 2002. Binding of Norwalk virus-like particles to ABH histo-blood group antigens is blocked by antisera from infected human volunteers or experimentally vaccinated mice. J. Virol. 76:12335-12343.[Abstract/Free Full Text]
    13. 13
  13. Harrington, P. R., J. Vinje, C. L. Moe, and R. S. Baric. 2004. Norovirus capture with histo-blood group antigens reveals novel virus-ligand interactions. J. Virol. 78:3035-3045.[Abstract/Free Full Text]
    14. 14
  14. Huang, P., T. Farkas, S. Marionneau, W. Zhong, N. Ruvoen-Clouet, A. L. Morrow, M. Altaye, L. K. Pickering, D. S. Newburg, J. LePendu, and X. Jiang. 2003. Noroviruses bind to human ABO, Lewis, and secretor histo-blood group antigens: identification of 4 distinct strain-specific patterns. J. Infect. Dis. 188:19-31.[CrossRef][Medline]
    15. 15
  15. Huang, P., T. Farkas, W. Zhong, M. Tan, S. Thornton, A. L. Morrow, and X. Jiang. 2005. 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. J. Virol. 79:6714-6722.[Abstract/Free Full Text]
    16. 16
  16. Hutson, A. M., R. L. Atmar, D. Y. Graham, and M. K. Estes. 2002. Norwalk virus infection and disease is associated with ABO histo-blood group type. J. Infect. Dis. 185:1335-1337.[CrossRef][Medline]
    17. 17
  17. Hutson, A. M., R. L. Atmar, D. M. Marcus, and M. K. Estes. 2003. Norwalk virus-like particle hemagglutination by binding to H histo-blood group antigens. J. Virol. 77:405-415.[CrossRef][Medline]
    18. 18
  18. Isshiki, S., A. Togayachi, T. Kudo, S. Nishihara, M. Watanabe, T. Kubota, M. Kitajima, N. Shiraishi, K. Sasaki, T. Andoh, and H. Narimatsu. 1999. Cloning, expression, and characterization of a novel UDP-galactose:beta-N-acetylglucosamine beta1,3-galactosyltransferase (beta3Gal-T5) responsible for synthesis of type 1 chain in colorectal and pancreatic epithelia and tumor cells derived therefrom. J. Biol. Chem. 274:12499-12507.[Abstract/Free Full Text]
    19. 19
  19. Ito, H., A. Kameyama, T. Sato, M. Sukegawa, H. K. Ishida, and H. Narimatsu. 2007. Strategy for the fine characterization of glycosyltransferase specificity using isotopomer assembly. Nat. Methods 4:577-582.[CrossRef][Medline]
    20. 20
  20. Kageyama, T., M. Shinohara, K. Uchida, S. Fukushi, F. B. Hoshino, S. Kojima, R. Takai, T. Oka, N. Takeda, and K. Katayama. 2004. Coexistence of multiple genotypes, including newly identified genotypes, in outbreaks of gastroenteritis due to Norovirus in Japan. J. Clin. Microbiol. 42:2988-2995.[Abstract/Free Full Text]
    21. 20
  21. Kamata, K., K. Shinozaki, M. Okada, Y. Seto, S. Kobayashi, K. Sakae, M. Oseto, K. Natori, H. Shirato-Horikoshi, K. Katayama, T. Tanaka, N. Takeda, and K. Taniguchi. 2005. Expression and antigenicity of virus-like particles of norovirus and their application for detection of noroviruses in stool samples. J. Med. Virol. 76:129-136.[CrossRef][Medline]
    22. 21
  22. Kaneko, M., S. Nishihara, N. Shinya, T. Kudo, H. Iwasaki, T. Seno, Y. Okubo, and H. Narimatsu. 1997. Wide variety of point mutations in the H gene of Bombay and para-Bombay individuals that inactivate H enzyme. Blood 90:839-849.[Abstract/Free Full Text]
    23. 22
  23. Kapikian, A. Z. 1996. Overview of viral gastroenteritis. Arch. Virol. Suppl. 12:7-19.[Medline]
    24. 22
  24. Kitamoto, N., T. Tanaka, K. Natori, N. Takeda, S. Nakata, X. Jiang, and M. K. Estes. 2002. Cross-reactivity among several recombinant calicivirus virus-like particles (VLPs) with monoclonal antibodies obtained from mice immunized orally with one type of VLP. J. Clin. Microbiol. 40:2459-2465.[Abstract/Free Full Text]
    25. 22
  25. Kobayashi, S., K. Sakae, Y. Suzuki, K. Shinozaki, M. Okada, H. Ishiko, K. Kamata, K. Suzuki, K. Natori, T. Miyamura, and N. Takeda. 2000. Molecular cloning, expression, and antigenicity of Seto virus belonging to genogroup I Norwalk-like viruses. J. Clin. Microbiol. 38:3492-3494.[Abstract/Free Full Text]
    26. 22
  26. Kobayashi, S., K. Sakae, K. Natori, N. Takeda, T. Miyamura, and Y. Suzuki. 2000. Serotype-specific antigen ELISA for detection of Chiba virus in stools. J. Med. Virol. 62:233-238.[CrossRef][Medline]
    27. 22
  27. Kobayashi, S., K. Sakae, Y. Suzuki, H. Ishiko, K. Kamata, K. Suzuki, K. Natori, T. Miyamura, and N. Takeda. 2000. Expression of recombinant capsid proteins of chitta virus, a genogroup II Norwalk virus, and development of an ELISA to detect the viral antigen. Microbiol. Immunol. 44:687-693.[Medline]
    28. 23
  28. Kudo, T., H. Iwasaki, S. Nishihara, N. Shinya, T. Ando, I. Narimatsu, and H. Narimatsu. 1996. Molecular genetic analysis of the human Lewis histo-blood group system. II. Secretor gene inactivation by a novel single missense mutation A385T in Japanese nonsecretor individuals. J. Biol. Chem. 271:9830-9837.[Abstract/Free Full Text]
    29. 24
  29. Lindesmith, L., C. Moe, S. Marionneau, N. Ruvoen, X. Jiang, L. Lindblad, P. Stewart, J. LePendu, and R. Baric. 2003. Human susceptibility and resistance to Norwalk virus infection. Nat. Med. 9:548-553.[CrossRef][Medline]
    30. 25
  30. Lopman, B., H. Vennema, E. Kohli, P. Pothier, A. Sanchez, A. Negredo, J. Buesa, E. Schreier, M. Reacher, D. Brown, J. Gray, M. Iturriza, C. Gallimore, B. Bottiger, K. O. Hedlund, M. Torven, C. H. von Bonsdorff, L. Maunula, M. Poljsak-Prijatelj, J. Zimsek, G. Reuter, G. Szucs, B. Melegh, L. Svennson, Y. van Duijnhoven, and M. Koopmans. 2004. Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant. Lancet 363:682-688.[CrossRef][Medline]
    31. 26
  31. Marionneau, S., N. Ruvoen, B. Le Moullac-Vaidye, M. Clement, A. Cailleau-Thomas, G. Ruiz-Palacois, P. Huang, X. Jiang, and J. Le Pendu. 2002. Norwalk virus binds to histo-blood group antigens present on gastroduodenal epithelial cells of secretor individuals. Gastroenterology 122:1967-1977.[CrossRef][Medline]
    32. 27
  32. Mollicone, R., J. Bara, J. Le Pendu, and R. Oriol. 1985. Immunohistologic pattern of type 1 (Lea, Leb) and type 2 (X, Y, H) blood group-related antigens in the human pyloric and duodenal mucosae. Lab. Investig. 53:219-227.[Medline]
    33. 28
  33. Narimatsu, H., S. Sinha, K. Brew, H. Okayama, and P. K. Qasba. 1986. Cloning and sequencing of cDNA of bovine N-acetylglucosamine (beta 1-4)galactosyltransferase. Proc. Natl. Acad. Sci. USA 83:4720-4724.[Abstract/Free Full Text]
    34. 29
  34. Noel, J. S., R. L. Fankhauser, T. Ando, S. S. Monroe, and R. I. Glass. 1999. Identification of a distinct common strain of "Norwalk-like viruses" having a global distribution. J. Infect. Dis. 179:1334-1344.[CrossRef][Medline]
    35. 30
  35. Okada, M., T. Ogawa, I. Kaiho, and K. Shinozaki. 2005. Genetic analysis of noroviruses in Chiba Prefecture, Japan, between 1999 and 2004. J. Clin. Microbiol. 43:4391-4401.[Abstract/Free Full Text]
    36. 31
  36. Oriol, R. 1990. Genetic control of the fucosylation of ABH precursor chains. Evidence for new epistatic interactions in different cells and tissues. J. Immunogenet. 17:235-245.[Medline]
    37. 32
  37. Oriol, R., J. Le Pendu, and R. Mollicone. 1986. Genetics of ABO, H, Lewis, X and related antigens. Vox Sang. 51:161-171.[Medline]
    38. 33
  38. Orntoft, T. F., E. H. Holmes, P. Johnson, S. Hakomori, and H. Clausen. 1991. Differential tissue expression of the Lewis blood group antigens: enzymatic, immunohistologic, and immunochemical evidence for Lewis a and b antigen expression in Le(a-b-) individuals. Blood 77:1389-1396.[Abstract/Free Full Text]
    39. 34
  39. Rockx, B. H., H. Vennema, C. J. Hoebe, E. Duizer, and M. P. Koopmans. 2005. Association of histo-blood group antigens and susceptibility to norovirus infections. J. Infect. Dis. 191:749-754.[CrossRef][Medline]
    40. 35
  40. Rogers, G. N., and J. C. Paulson. 1983. Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology 127:361-373.[CrossRef][Medline]
    41. 36
  41. Rogers, G. N., T. J. Pritchett, J. L. Lane, and J. C. Paulson. 1983. Differential sensitivity of human, avian, and equine influenza A viruses to a glycoprotein inhibitor of infection: selection of receptor specific variants. Virology 131:394-408.[CrossRef][Medline]
    42. 37
  42. Sakamoto, J., K. Furukawa, C. Cordon-Cardo, B. W. Yin, W. J. Rettig, H. F. Oettgen, L. J. Old, and K. O. Lloyd. 1986. Expression of Lewisa, Lewisb, X, and Y blood group antigens in human colonic tumors and normal tissue and in human tumor-derived cell lines. Cancer Res. 46:1553-1561.[Abstract/Free Full Text]
    43. 38
  43. Shiraishi, N., A. Natsume, A. Togayachi, T. Endo, T. Akashima, Y. Yamada, N. Imai, S. Nakagawa, S. Koizumi, S. Sekine, H. Narimatsu, and K. Sasaki. 2001. Identification and characterization of three novel beta 1,3-N-acetylglucosaminyltransferases structurally related to the beta 1,3-galactosyltransferase family. J. Biol. Chem. 276:3498-3507.[Abstract/Free Full Text]
    44. 39
  44. Shirato-Horikoshi, H., S. Ogawa, T. Wakita, N. Takeda, and G. S. Hansman. 2007. Binding activity of norovirus and sapovirus to histo-blood group antigens. Arch. Virol. 152:457-461.[CrossRef][Medline]
    45. 40
  45. Sidmann, F. K. (ed.). 1981. Appendix 2: saliva testing for ABH and Lewis, p. 122-123. In Technical Manual of the American Association of Blood Banks, 8th ed. J. B. Lippincott, Philadelphia, PA.
    46. 41
  46. Soejima, M., and Y. Koda. 2005. Molecular mechanisms of Lewis antigen expression. Leg. Med. (Tokyo) 7:266-269.[Medline]
    47. 41
  47. Tamura, M., K. Natori, M. Kobayashi, T. Miyamura, and N. Takeda. 2000. Interaction of recombinant Norwalk virus particles with the 105-kilodalton cellular binding protein, a candidate receptor molecule for virus attachment. J. Virol. 74:11589-11597.[Abstract/Free Full Text]
    48. 42
  48. Tan, M., P. Huang, J. Meller, W. Zhong, T. Farkas, and X. Jiang. 2003. Mutations within the P2 domain of norovirus capsid affect binding to human histo-blood group antigens: evidence for a binding pocket. J. Virol. 77:12562-12571.[Abstract/Free Full Text]

Journal of Virology, November 2008, p. 10756-10767, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00802-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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