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Nathalie Ruvoenclouet - One of the best experts on this subject based on the ideXlab platform.
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histo blood group antigen binding specificities of human rotaviruses are associated with gastroenteritis but not with in vitro infection
Scientific Reports, 2018Co-Authors: Laure Barbe, Johan Nordgren, Lennart Svensson, Beatrice Le Moullacvaidye, Nathalie Ruvoenclouet, K Echasserieau, Karine Bernardeau, Thomas Carton, Nicolai V BovinAbstract:Human strains of rotavirus A (RVAs) recognize fucosylated glycans belonging to histo-blood group antigens (HBGAs) through their spike protein VP8*. Lack of these ligands due to genetic polymorphisms is associated with resistance to gastroenteritis caused by P[8] genotype RVAs. With the aim to delineate the contribution of HBGAs in the process, we analyzed the glycan specificity of VP8* proteins from various P genotypes. Binding to saliva of VP8* from P[8] and P[4] genotypes required expression of both FUT2 and FUT3 enzymes, whilst binding of VP8* from the P[14] genotype required FUT2 and A enzymes. We further defined a glycan motif, GlcNAcβ3Galβ4GlcNAc, recognized by P[6] clinical strains. Conversion into Lewis antigens by the FUT3 enzyme impaired recognition, explaining their lower binding to saliva of Lewis positive phenotype. In addition, the presence of neutralizing antibodies was associated with the presence of the FUT2 wild type allele in sera from young healthy adults. Nonetheless, in vitro infection of transformed cell lines was independent of HBGAs expression, indicating that HBGAs are not human RV receptors. The match between results from saliva-based binding assays and the epidemiological data indicates that the polymorphism of human HBGAs controls susceptibility to RVAs, although the exact mechanism remains unclear.
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noroviruses and histo blood groups the impact of common host genetic polymorphisms on virus transmission and evolution
Reviews in Medical Virology, 2013Co-Authors: Nathalie Ruvoenclouet, Gael Belliot, Jacques Le PenduAbstract:Noroviruses (NoVs) are recognized as a leading cause of human gastroenteritis worldwide. Infection occurs following the ingestion of contaminated food or, most often, through direct contact from person to person. However, not all individuals are equally sensitive to these viruses. Indeed, NoVs use glycans of the ABH and Lewis histo-blood group antigen family (HBGAs) as attachment factors. At the epithelial level, the synthesis of these HBGAs requires the action of several glycosyltransferases that are encoded by the ABO, FUT2, and FUT3 genes. The combined polymorphism at these three loci dictates sensitivity to NoV infection because the attachment profile to these glycans varies among strains. Structural analysis of the capsid protein interaction with HBGAs reveals distinct modes of binding for strains of genogroups I and II but high conservation within each genogroup, whereas minor amino acid changes are sufficient to generate modifications of HBGA-binding specificities or affinities. Such modifications therefore induce changes in the spectrum of susceptible individuals. Studies of NoV-HBGA interactions together with phylogenetic analyses and the epidemiologic survey of strains indicate that NoV transmission and evolution depend on both the establishment of herd immunity and the genetic resistance of many individuals, which confers herd innate protection by restricting NoV circulation.
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association between expression of the h histo blood group antigen α1 2fucosyltransferases polymorphism of wild rabbits and sensitivity to rabbit hemorrhagic disease virus
Glycobiology, 2008Co-Authors: Patrice Guillon, Beatrice Le Moullacvaidye, Nathalie Ruvoenclouet, Stephane Marchandeau, Jacques Le PenduAbstract:RHDV (rabbit hemorrhagic disease virus) is a highly virulent calicivirus that has become a major cause of mortality in wild rabbit populations (Oryctolagus cuniculus). It binds to the histo-blood group antigen (HBGA) H type 2 which requires an alpha1,2fucosyltransferase for its synthesis. In rabbit, three alpha1,2fucosyltransferases genes are known, FUT1, Fut2, and Sec1. Nonfunctional alleles at any of these loci could potentially confer resistance to RHDV, similar to human FUT2 alleles that determine the nonsecretor phenotype and resistance to infection by various NoV strains. In this study, we looked for the presence of H type 2 on buccal epithelial cells of wild rabbits from two geographic areas under RHDV pressure and from one RHDV-free area. Some animals with diminished H type 2 expression were found in the three populations (nonsecretor-like phenotype). Their frequency markedly increased according to the RHDV impact, suggesting that outbreaks selected survivors with low expression of the virus ligand. Polymorphisms of the FUT1, Fut2, and Sec1 coding regions were determined among animals that either died or survived outbreaks. The Fut2 and Sec1 genes presented a high polymorphism and the frequency of one Sec1 allele was significantly elevated, over 6-fold, among survivors. Sec1 enzyme variants showed either moderate, low, or undetectable catalytic activity, whereas all variant Fut2 enzymes showed strong catalytic activity. This functional analysis of the enzymes encoded by each Fut2 and Sec1 allele suggests that the association between one Sec1 allele and survival might be explained by a deficit of alpha1,2fucosyltransferase expression rather than by impaired catalytic activity.
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influence of the combined abo fut2 and fut3 polymorphism on susceptibility to norwalk virus attachment
The Journal of Infectious Diseases, 2005Co-Authors: Severine Marionneau, Nathalie Ruvoenclouet, Nicolai V Bovin, Jacques Le Pendu, Fabrice AiraudAbstract:4 Shemyakin Institute of Bioorganic Chemistry, Moscow, Russia The binding of Norwalk virus (NV) recombinant capsids was tested in a panel of saliva samples collected from 96 donors with different ABO, secretor, and Lewis phenotypes. As previously reported, binding occurred specifically to saliva from secretors, regardless of their Lewis phenotype status. Blood group B saliva was poorly recognized, whereas binding to blood group O saliva was higher and binding to blood group A saliva was highest. Transfection of either blood group A or B enzyme into H epitope-expressing cells showed that masking of H epitopes by the A and B antigens blocked the attachment of NV capsids. The high level of binding to blood group A secretor saliva could be explained by an optimal H type 1 ligand density, which was lower than that in blood group O saliva and much higher than that in blood group B saliva. Indeed, despite a higher ligand density, saliva from homozygotes with 2 functional FUT2 alleles was less strongly recognized than saliva from heterozygotes with 1 functional and 1 inactivated FUT2 allele. Partial fucosidase treatment of duodenal tissue sections and binding to a synthetic probe with varying densities of H type 1 trisaccharide indicated that optimal attachment occurred at medium ligand density.
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influence of the combined abo fut2 and fut3 polymorphism on susceptibility to norwalk virus attachment
The Journal of Infectious Diseases, 2005Co-Authors: Severine Marionneau, Nathalie Ruvoenclouet, Nicolai V Bovin, Jacques Le Pendu, Fabrice AiraudAbstract:The binding of Norwalk virus (NV) recombinant capsids was tested in a panel of saliva samples collected from 96 donors with different ABO, secretor, and Lewis phenotypes. As previously reported, binding occurred specifically to saliva from secretors, regardless of their Lewis phenotype status. Blood group B saliva was poorly recognized, whereas binding to blood group O saliva was higher and binding to blood group A saliva was highest. Transfection of either blood group A or B enzyme into H epitope-expressing cells showed that masking of H epitopes by the A and B antigens blocked the attachment of NV capsids. The high level of binding to blood group A secretor saliva could be explained by an optimal H type 1 ligand density, which was lower than that in blood group O saliva and much higher than that in blood group B saliva. Indeed, despite a higher ligand density, saliva from homozygotes with 2 functional FUT2 alleles was less strongly recognized than saliva from heterozygotes with 1 functional and 1 inactivated FUT2 allele. Partial fucosidase treatment of duodenal tissue sections and binding to a synthetic probe with varying densities of H type 1 trisaccharide indicated that optimal attachment occurred at medium ligand density.
Yoshiro Koda - One of the best experts on this subject based on the ideXlab platform.
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taqman real time polymerase chain reaction for detection of sec1 fut2 hybrid alleles identification of novel hybrid allele
Clinica Chimica Acta, 2013Co-Authors: Mikiko Soejima, Yoshiro KodaAbstract:Abstract Background Two hybrid alleles between the secretor type α(1,2)fucosyltransferase gene (FUT2) and a pseudogene of FUT2 (SEC1) have been reported so far; parts of the SEC1 and FUT2 sequences are suggested to be susceptible to recombination. The sefus, one of the two hybrid alleles, is found in Japanese populations at relative high frequencies. Methods A TaqMan assay to distinguish SEC1 and SEC1-FUT2 hybrid alleles was designed for the purpose of dealing with large number of samples. Results The results of the present method were fully consistent with those of the previous method for detection of sefus in the Japanese population. In addition, a novel SEC1-FUT2-SEC1 hybrid allele, which contains a 35-bp sequence (between positions 418 and 452) that is identical to the FUT2 sequence including a 13-bp FUT2-specific region (between positions 436 and 448), was encountered in an individual of European descent. Conclusions The present TaqMan assay is a reliable and powerful method for the large scale association study between disease susceptibility and FUT2 genotypes especially in the Japanese populations because of relative high frequency of sefus. In addition, this method is a useful tool to find novel SEC1-FUT2 hybrid alleles.
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TaqMan-based real-time polymerase chain reaction for detection of FUT2 copy number variations: identification of novel Alu-mediated deletion.
Transfusion, 2010Co-Authors: Mikiko Soejima, Yoshiro KodaAbstract:BACKGROUND: The human FUT2 locus, which encodes a secretor-type α(1,2)fucosyltransferase, is known to be highly polymorphic. In addition to many single-nucleotide polymorphisms, three recombination alleles with a deletion of complete or partial FUT2 coding region have been reported. STUDY DESIGN AND METHODS: To detect copy number variations (CNVs) of the FUT2 gene including three recombinant alleles by a high-throughput system, we developed a triplex TaqMan real-time polymerase chain reaction (PCR) method. The relative number of copies of two regions of the FUT2 gene, the 5′ flanking (FUT2-5′) and FUT2-promoter (Prom) regions, were determined by comparing the number of threshold cycles (Ct) to those of the albumin gene (ALB) as the internal control (ΔCt). RESULTS: The mean 2−ΔΔCt values (FUT2-5′/ALB or Prom/ALB) obtained from 237 samples with known FUT2 copy numbers clearly differentiated two nonoverlapping intervals that corresponded to the one-copy-number samples ranging from 0.42 to 0.59 and two-copy-number samples ranging from 0.81 to 1.19; no FUT2-5′ signal for recombination alleles was detected in homozygotes. Using this assay, we detected an individual in a Chinese population with a loss of one copy of the FUT2-5′ region resulting from a novel Alu-mediated FUT2 deletion (approx. 4 kb). CONCLUSIONS: The TaqMan real-time PCR method was able to detect the number of copies of FUT2 and distinguish different kinds of known CNVs. This system is robust, fast, and suitable for high-throughput analysis.
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sec1 fut2 sec1 hybrid allele generated by interlocus gene conversion
Transfusion, 2008Co-Authors: Mikiko Soejima, Junko Fujihara, Haruo Takeshita, Yoshiro KodaAbstract:BACKGROUND: Many single-nucleotide polymorphisms have been identified in the coding region of the FUT2 locus, which encodes secretor type α(1,2)fucosyltransferase. In addition, three recombination alleles have been reported. Of these recombination alleles, a fusion gene generated by an unequal crossing over between Sec1, a pseudogene that locates 23 kb upstream to and has high sequence homology with FUT2 and FUT2, was identified as a Japanese-specific nonsecretor allele (sefus). STUDY DESIGN AND METHODS: During the screening of the sefus in Mongolians (n = 118), a hybrid allele of Sec1-FUT2-Sec1 was found. RESULTS: The DNA sequence suggested that the Sec1-FUT2-Sec1 allele contains a 275-bp sequence (between positions 259 and 533) that is identical to the FUT2 sequence including a 54-bp FUT2-specific region (between positions 417 and 470) and that might have been generated by an interlocus gene conversion. CONCLUSION: Because the recombination region of sefus and the upstream recombination region of Sec1-FUT2-Sec1 are almost identical, this sequence stretch is likely to be the breakpoint for different kinds of recombinations that occur in this family of genes.
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contrasting patterns of polymorphisms at the abo secretor gene fut2 and plasma alpha 1 3 fucosyltransferase gene fut6 in human populations
Genetics, 2001Co-Authors: Yoshiro Koda, Mikiko Soejima, Hao Pang, Hidenori Tachida, Yuhua Liu, Abbas Ghaderi, Osamu Takenaka, Hiroshi KimuraAbstract:The coding sequences ( approximately 1 kb) of FUT2 [ABO-Secretor type alpha(1,2)fucosyltransferase] and of FUT6 [plasma alpha(1,3)fucosyltransferase] were analyzed for allelic polymorphism by direct sequencing in five populations. The nucleotide diversities of FUT2 estimated from pairwise sequence differences were 0.0045, 0.0042, 0.0042, 0.0009, and 0.0008 in Africans, European-Africans, Iranians, Chinese, and Japanese, respectively. The nucleotide diversities of FUT6 were 0.0024, 0.0016, 0.0015, 0.0017, and 0.0020 in Africans, European-Africans, Iranians, Chinese, and Japanese, respectively. At FUT2, excesses in pairwise sequence differences compared to the number of polymorphic sites as indicated by a significantly positive Tajima's D were observed in European-Africans and in Iranians. The data do not fit expectations of the equilibrium neutral model with an infinite number of sites. On the other hand, Tajima's D's at FUT6 in each of the five populations and at FUT2 in Africans, Chinese, and Japanese were not significantly different from zero. F(ST) between the Asians and the others measured at FUT2 was higher than at FUT6. These results suggest that natural selection was responsible for the generation of the FUT2 polymorphism in European-Africans and in Iranians.
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two distinct alu mediated deletions of the human abo secretor fut2 locus in samoan and bangladeshi populations
Human Mutation, 2000Co-Authors: Hao Pang, Mikiko Soejima, Yoshiro Koda, Noboru Fujitani, Mohammed Nasimul Islam, A Shamsul K M Islam, Hiroshi KimuraAbstract:The human secretor α(1,2) fucosyltransferase encoded by the FUT2 determines the production of ABO(H) antigens in secretions. Recent studies demonstrated the presence of several nonfunctional alleles in the FUT2. During the analysis for inactivating mutations at the FUT2 locus from 24 Samoan and 47 Bangladeshi individuals, we found two distinct Alu-mediated deletions of FUT2. The FUT2 deletion in a Bangladeshi population was identical with that found in Indian individuals with the Bombay phenotype (sedel), but not associated with the null allele (T725G) of the H gene (FUT1). The FUT2 deletion in Samoans is a novel null allele (sedel2). The junction region of sedel2 was successfully amplified using the same primers for the sedel amplification. DNA sequencing of the junction region of the sedel2 indicated that there was a 32-bp sequence identity between DNA sequences surrounding the 5′ and 3′ breakpoints. The size of the deletion of the sedel2 was 9.3 kb, including the full coding region of FUT2. The frequency of the sedel in a Bangladeshi population was 0.074, and that of the sedel2 in a Samoan population was 0.104. Hum Mutat 16:274, 2000. © 2000 Wiley-Liss, Inc.
Mikiko Soejima - One of the best experts on this subject based on the ideXlab platform.
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taqman real time polymerase chain reaction for detection of sec1 fut2 hybrid alleles identification of novel hybrid allele
Clinica Chimica Acta, 2013Co-Authors: Mikiko Soejima, Yoshiro KodaAbstract:Abstract Background Two hybrid alleles between the secretor type α(1,2)fucosyltransferase gene (FUT2) and a pseudogene of FUT2 (SEC1) have been reported so far; parts of the SEC1 and FUT2 sequences are suggested to be susceptible to recombination. The sefus, one of the two hybrid alleles, is found in Japanese populations at relative high frequencies. Methods A TaqMan assay to distinguish SEC1 and SEC1-FUT2 hybrid alleles was designed for the purpose of dealing with large number of samples. Results The results of the present method were fully consistent with those of the previous method for detection of sefus in the Japanese population. In addition, a novel SEC1-FUT2-SEC1 hybrid allele, which contains a 35-bp sequence (between positions 418 and 452) that is identical to the FUT2 sequence including a 13-bp FUT2-specific region (between positions 436 and 448), was encountered in an individual of European descent. Conclusions The present TaqMan assay is a reliable and powerful method for the large scale association study between disease susceptibility and FUT2 genotypes especially in the Japanese populations because of relative high frequency of sefus. In addition, this method is a useful tool to find novel SEC1-FUT2 hybrid alleles.
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TaqMan-based real-time polymerase chain reaction for detection of FUT2 copy number variations: identification of novel Alu-mediated deletion.
Transfusion, 2010Co-Authors: Mikiko Soejima, Yoshiro KodaAbstract:BACKGROUND: The human FUT2 locus, which encodes a secretor-type α(1,2)fucosyltransferase, is known to be highly polymorphic. In addition to many single-nucleotide polymorphisms, three recombination alleles with a deletion of complete or partial FUT2 coding region have been reported. STUDY DESIGN AND METHODS: To detect copy number variations (CNVs) of the FUT2 gene including three recombinant alleles by a high-throughput system, we developed a triplex TaqMan real-time polymerase chain reaction (PCR) method. The relative number of copies of two regions of the FUT2 gene, the 5′ flanking (FUT2-5′) and FUT2-promoter (Prom) regions, were determined by comparing the number of threshold cycles (Ct) to those of the albumin gene (ALB) as the internal control (ΔCt). RESULTS: The mean 2−ΔΔCt values (FUT2-5′/ALB or Prom/ALB) obtained from 237 samples with known FUT2 copy numbers clearly differentiated two nonoverlapping intervals that corresponded to the one-copy-number samples ranging from 0.42 to 0.59 and two-copy-number samples ranging from 0.81 to 1.19; no FUT2-5′ signal for recombination alleles was detected in homozygotes. Using this assay, we detected an individual in a Chinese population with a loss of one copy of the FUT2-5′ region resulting from a novel Alu-mediated FUT2 deletion (approx. 4 kb). CONCLUSIONS: The TaqMan real-time PCR method was able to detect the number of copies of FUT2 and distinguish different kinds of known CNVs. This system is robust, fast, and suitable for high-throughput analysis.
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sec1 fut2 sec1 hybrid allele generated by interlocus gene conversion
Transfusion, 2008Co-Authors: Mikiko Soejima, Junko Fujihara, Haruo Takeshita, Yoshiro KodaAbstract:BACKGROUND: Many single-nucleotide polymorphisms have been identified in the coding region of the FUT2 locus, which encodes secretor type α(1,2)fucosyltransferase. In addition, three recombination alleles have been reported. Of these recombination alleles, a fusion gene generated by an unequal crossing over between Sec1, a pseudogene that locates 23 kb upstream to and has high sequence homology with FUT2 and FUT2, was identified as a Japanese-specific nonsecretor allele (sefus). STUDY DESIGN AND METHODS: During the screening of the sefus in Mongolians (n = 118), a hybrid allele of Sec1-FUT2-Sec1 was found. RESULTS: The DNA sequence suggested that the Sec1-FUT2-Sec1 allele contains a 275-bp sequence (between positions 259 and 533) that is identical to the FUT2 sequence including a 54-bp FUT2-specific region (between positions 417 and 470) and that might have been generated by an interlocus gene conversion. CONCLUSION: Because the recombination region of sefus and the upstream recombination region of Sec1-FUT2-Sec1 are almost identical, this sequence stretch is likely to be the breakpoint for different kinds of recombinations that occur in this family of genes.
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contrasting patterns of polymorphisms at the abo secretor gene fut2 and plasma alpha 1 3 fucosyltransferase gene fut6 in human populations
Genetics, 2001Co-Authors: Yoshiro Koda, Mikiko Soejima, Hao Pang, Hidenori Tachida, Yuhua Liu, Abbas Ghaderi, Osamu Takenaka, Hiroshi KimuraAbstract:The coding sequences ( approximately 1 kb) of FUT2 [ABO-Secretor type alpha(1,2)fucosyltransferase] and of FUT6 [plasma alpha(1,3)fucosyltransferase] were analyzed for allelic polymorphism by direct sequencing in five populations. The nucleotide diversities of FUT2 estimated from pairwise sequence differences were 0.0045, 0.0042, 0.0042, 0.0009, and 0.0008 in Africans, European-Africans, Iranians, Chinese, and Japanese, respectively. The nucleotide diversities of FUT6 were 0.0024, 0.0016, 0.0015, 0.0017, and 0.0020 in Africans, European-Africans, Iranians, Chinese, and Japanese, respectively. At FUT2, excesses in pairwise sequence differences compared to the number of polymorphic sites as indicated by a significantly positive Tajima's D were observed in European-Africans and in Iranians. The data do not fit expectations of the equilibrium neutral model with an infinite number of sites. On the other hand, Tajima's D's at FUT6 in each of the five populations and at FUT2 in Africans, Chinese, and Japanese were not significantly different from zero. F(ST) between the Asians and the others measured at FUT2 was higher than at FUT6. These results suggest that natural selection was responsible for the generation of the FUT2 polymorphism in European-Africans and in Iranians.
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two distinct alu mediated deletions of the human abo secretor fut2 locus in samoan and bangladeshi populations
Human Mutation, 2000Co-Authors: Hao Pang, Mikiko Soejima, Yoshiro Koda, Noboru Fujitani, Mohammed Nasimul Islam, A Shamsul K M Islam, Hiroshi KimuraAbstract:The human secretor α(1,2) fucosyltransferase encoded by the FUT2 determines the production of ABO(H) antigens in secretions. Recent studies demonstrated the presence of several nonfunctional alleles in the FUT2. During the analysis for inactivating mutations at the FUT2 locus from 24 Samoan and 47 Bangladeshi individuals, we found two distinct Alu-mediated deletions of FUT2. The FUT2 deletion in a Bangladeshi population was identical with that found in Indian individuals with the Bombay phenotype (sedel), but not associated with the null allele (T725G) of the H gene (FUT1). The FUT2 deletion in Samoans is a novel null allele (sedel2). The junction region of sedel2 was successfully amplified using the same primers for the sedel amplification. DNA sequencing of the junction region of the sedel2 indicated that there was a 32-bp sequence identity between DNA sequences surrounding the 5′ and 3′ breakpoints. The size of the deletion of the sedel2 was 9.3 kb, including the full coding region of FUT2. The frequency of the sedel in a Bangladeshi population was 0.074, and that of the sedel2 in a Samoan population was 0.104. Hum Mutat 16:274, 2000. © 2000 Wiley-Liss, Inc.
Jacques Le Pendu - One of the best experts on this subject based on the ideXlab platform.
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fut2 secretor status and fut3 polymorphisms of children with acute diarrhea infected with rotavirus and norovirus in brazil
Viruses, 2020Co-Authors: Marco Andre Loureiro Tonini, Beatrice Le Moullacvaidye, Jacques Le Pendu, Debora Maria Pires Goncalves Barreira, Luciana Bueno De Freitas Santolin, Lays Paula Bondi Volpini, Jose Paulo Gagliardi Leite, Liliana Cruz SpanoAbstract:Host susceptibility according to human histo-blood group antigens (HBGAs) is widely known for norovirus infection, but is less described for rotavirus. Due to the variable HBGA polymorphism among populations, we aimed to evaluate the association between HBGA phenotypes (ABH, Lewis and secretor status) and susceptibility to rotavirus and norovirus symptomatic infection, and the polymorphisms of FUT2 and FUT3, of children from southeastern Brazil. Paired fecal-buccal specimens from 272 children with acute diarrhea were used to determine rotavirus/norovirus genotypes and HBGAs phenotypes/genotypes, respectively. Altogether, 100 (36.8%) children were infected with rotavirus and norovirus. The rotavirus P[8] genotype predominates (85.7%). Most of the noroviruses (93.8%) belonged to genogroup II (GII). GII.4 Sydney represented 76% (35/46) amongst five other genotypes. Rotavirus and noroviruses infected predominantly children with secretor status (97% and 98.5%, respectively). However, fewer rotavirus-infected children were Lewis-negative (8.6%) than the norovirus-infected ones (18.5%). FUT3 single nucleotide polymorphisms (SNP) occurred mostly at the T59G > G508A > T202C > C314T positions. Our results reinforce the current knowledge that secretors are more susceptible to infection by both rotavirus and norovirus than non-secretors. The high rate for Lewis negative (17.1%) and the combination of SNPs, beyond the secretor status, may reflect the highly mixed population in Brazil.
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noroviruses and histo blood groups the impact of common host genetic polymorphisms on virus transmission and evolution
Reviews in Medical Virology, 2013Co-Authors: Nathalie Ruvoenclouet, Gael Belliot, Jacques Le PenduAbstract:Noroviruses (NoVs) are recognized as a leading cause of human gastroenteritis worldwide. Infection occurs following the ingestion of contaminated food or, most often, through direct contact from person to person. However, not all individuals are equally sensitive to these viruses. Indeed, NoVs use glycans of the ABH and Lewis histo-blood group antigen family (HBGAs) as attachment factors. At the epithelial level, the synthesis of these HBGAs requires the action of several glycosyltransferases that are encoded by the ABO, FUT2, and FUT3 genes. The combined polymorphism at these three loci dictates sensitivity to NoV infection because the attachment profile to these glycans varies among strains. Structural analysis of the capsid protein interaction with HBGAs reveals distinct modes of binding for strains of genogroups I and II but high conservation within each genogroup, whereas minor amino acid changes are sufficient to generate modifications of HBGA-binding specificities or affinities. Such modifications therefore induce changes in the spectrum of susceptible individuals. Studies of NoV-HBGA interactions together with phylogenetic analyses and the epidemiologic survey of strains indicate that NoV transmission and evolution depend on both the establishment of herd immunity and the genetic resistance of many individuals, which confers herd innate protection by restricting NoV circulation.
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molecular characterization of noroviruses and hbga from infected quilombola children in espirito santo state brazil
PLOS ONE, 2013Co-Authors: Fernando Vicentini, Beatrice Le Moullacvaidye, Jacques Le Pendu, Wilson Denadai, Yohanna Mayelle Gomes, Tatiana Lundgren Rose, Monica Simoes Rocha Ferreira, Jose Paulo Gagliardi LeiteAbstract:Noroviruses (NoV) are the main etiological agents of gastroenteritis outbreaks worldwide and susceptibility to NoV infection has been related to the histo-blood group antigen (HBGA). This study aimed to determine the prevalence of NoV strains and to evaluate the HBGA phenotype and genotype of children from semi-isolated Quilombola communities, descendents of black slaves in Brazil. A total of 397 children up to eleven years old, with and without diarrhea, from Quilombola Communities in the Espirito Santo State, Brazil, were investigated for the presence of NoV from August 2007 to September 2009. Feces were collected from all the children, and blood from the NoV positive children. NoV was screened by reverse transcription-PCR with primers for the RNA-dependent RNA polymerase region; genogroup was determined by PCR with primers for the C and D regions and genotyped by sequencing. HBGA phenotype was performed by gel-spinning and FUT2 and FUT3 were analyzed by PCR or sequencing analysis. NoV were detected in 9.2% (12/131) of diarrheic and 1.5% (4/266) of non-diarrheic children (p,0.05, Fisher’s exact test). GI and GII genogroups were present in 12.5% and 87.5% of the samples, respectively. The following genotypes were characterized: GII.4 (25%), GII.12 (25%), GII.6 (12.5%) and GI.1 (6.3%), GI.3 (12.5%) and GI.4 (6.3%). Children infected with NoV showed the A (n = 6), O (n = 6), and B (n = 2) HBGA phenotypes, and 13 of them were classified as secretors (Se) and one as a non secretor (se). Mutations of Se40, 171,216,357,428,739,960 were found for the FUT2 gene and mutations of Le59, 202, 314 for the FUT3 gene. The only se child was infected by NoV GI, whereas the Se children were indiscriminately infected by GI or GII. This study showed rates of NoV infection in symptomatic and asymptomatic Quilombola children consistent with other studies. However, children under 12 months were seven times more affected than those between 1 and 5 years old. GII.12 was as frequent as GII.4 and GI.1 and GI.4 were described for the first time in Brazil. Owing to the small number of cases studied, no clear pattern of susceptibility and/or HBGA resistance could be inferred.
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association between expression of the h histo blood group antigen α1 2fucosyltransferases polymorphism of wild rabbits and sensitivity to rabbit hemorrhagic disease virus
Glycobiology, 2008Co-Authors: Patrice Guillon, Beatrice Le Moullacvaidye, Nathalie Ruvoenclouet, Stephane Marchandeau, Jacques Le PenduAbstract:RHDV (rabbit hemorrhagic disease virus) is a highly virulent calicivirus that has become a major cause of mortality in wild rabbit populations (Oryctolagus cuniculus). It binds to the histo-blood group antigen (HBGA) H type 2 which requires an alpha1,2fucosyltransferase for its synthesis. In rabbit, three alpha1,2fucosyltransferases genes are known, FUT1, Fut2, and Sec1. Nonfunctional alleles at any of these loci could potentially confer resistance to RHDV, similar to human FUT2 alleles that determine the nonsecretor phenotype and resistance to infection by various NoV strains. In this study, we looked for the presence of H type 2 on buccal epithelial cells of wild rabbits from two geographic areas under RHDV pressure and from one RHDV-free area. Some animals with diminished H type 2 expression were found in the three populations (nonsecretor-like phenotype). Their frequency markedly increased according to the RHDV impact, suggesting that outbreaks selected survivors with low expression of the virus ligand. Polymorphisms of the FUT1, Fut2, and Sec1 coding regions were determined among animals that either died or survived outbreaks. The Fut2 and Sec1 genes presented a high polymorphism and the frequency of one Sec1 allele was significantly elevated, over 6-fold, among survivors. Sec1 enzyme variants showed either moderate, low, or undetectable catalytic activity, whereas all variant Fut2 enzymes showed strong catalytic activity. This functional analysis of the enzymes encoded by each Fut2 and Sec1 allele suggests that the association between one Sec1 allele and survival might be explained by a deficit of alpha1,2fucosyltransferase expression rather than by impaired catalytic activity.
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influence of the combined abo fut2 and fut3 polymorphism on susceptibility to norwalk virus attachment
The Journal of Infectious Diseases, 2005Co-Authors: Severine Marionneau, Nathalie Ruvoenclouet, Nicolai V Bovin, Jacques Le Pendu, Fabrice AiraudAbstract:4 Shemyakin Institute of Bioorganic Chemistry, Moscow, Russia The binding of Norwalk virus (NV) recombinant capsids was tested in a panel of saliva samples collected from 96 donors with different ABO, secretor, and Lewis phenotypes. As previously reported, binding occurred specifically to saliva from secretors, regardless of their Lewis phenotype status. Blood group B saliva was poorly recognized, whereas binding to blood group O saliva was higher and binding to blood group A saliva was highest. Transfection of either blood group A or B enzyme into H epitope-expressing cells showed that masking of H epitopes by the A and B antigens blocked the attachment of NV capsids. The high level of binding to blood group A secretor saliva could be explained by an optimal H type 1 ligand density, which was lower than that in blood group O saliva and much higher than that in blood group B saliva. Indeed, despite a higher ligand density, saliva from homozygotes with 2 functional FUT2 alleles was less strongly recognized than saliva from heterozygotes with 1 functional and 1 inactivated FUT2 allele. Partial fucosidase treatment of duodenal tissue sections and binding to a synthetic probe with varying densities of H type 1 trisaccharide indicated that optimal attachment occurred at medium ligand density.
Hiroshi Kimura - One of the best experts on this subject based on the ideXlab platform.
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contrasting patterns of polymorphisms at the abo secretor gene fut2 and plasma alpha 1 3 fucosyltransferase gene fut6 in human populations
Genetics, 2001Co-Authors: Yoshiro Koda, Mikiko Soejima, Hao Pang, Hidenori Tachida, Yuhua Liu, Abbas Ghaderi, Osamu Takenaka, Hiroshi KimuraAbstract:The coding sequences ( approximately 1 kb) of FUT2 [ABO-Secretor type alpha(1,2)fucosyltransferase] and of FUT6 [plasma alpha(1,3)fucosyltransferase] were analyzed for allelic polymorphism by direct sequencing in five populations. The nucleotide diversities of FUT2 estimated from pairwise sequence differences were 0.0045, 0.0042, 0.0042, 0.0009, and 0.0008 in Africans, European-Africans, Iranians, Chinese, and Japanese, respectively. The nucleotide diversities of FUT6 were 0.0024, 0.0016, 0.0015, 0.0017, and 0.0020 in Africans, European-Africans, Iranians, Chinese, and Japanese, respectively. At FUT2, excesses in pairwise sequence differences compared to the number of polymorphic sites as indicated by a significantly positive Tajima's D were observed in European-Africans and in Iranians. The data do not fit expectations of the equilibrium neutral model with an infinite number of sites. On the other hand, Tajima's D's at FUT6 in each of the five populations and at FUT2 in Africans, Chinese, and Japanese were not significantly different from zero. F(ST) between the Asians and the others measured at FUT2 was higher than at FUT6. These results suggest that natural selection was responsible for the generation of the FUT2 polymorphism in European-Africans and in Iranians.
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two distinct alu mediated deletions of the human abo secretor fut2 locus in samoan and bangladeshi populations
Human Mutation, 2000Co-Authors: Hao Pang, Mikiko Soejima, Yoshiro Koda, Noboru Fujitani, Mohammed Nasimul Islam, A Shamsul K M Islam, Hiroshi KimuraAbstract:The human secretor α(1,2) fucosyltransferase encoded by the FUT2 determines the production of ABO(H) antigens in secretions. Recent studies demonstrated the presence of several nonfunctional alleles in the FUT2. During the analysis for inactivating mutations at the FUT2 locus from 24 Samoan and 47 Bangladeshi individuals, we found two distinct Alu-mediated deletions of FUT2. The FUT2 deletion in a Bangladeshi population was identical with that found in Indian individuals with the Bombay phenotype (sedel), but not associated with the null allele (T725G) of the H gene (FUT1). The FUT2 deletion in Samoans is a novel null allele (sedel2). The junction region of sedel2 was successfully amplified using the same primers for the sedel amplification. DNA sequencing of the junction region of the sedel2 indicated that there was a 32-bp sequence identity between DNA sequences surrounding the 5′ and 3′ breakpoints. The size of the deletion of the sedel2 was 9.3 kb, including the full coding region of FUT2. The frequency of the sedel in a Bangladeshi population was 0.074, and that of the sedel2 in a Samoan population was 0.104. Hum Mutat 16:274, 2000. © 2000 Wiley-Liss, Inc.
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missense mutation of FUT1 and deletion of fut2 are responsible for indian bombay phenotype of abo blood group system
Biochemical and Biophysical Research Communications, 1997Co-Authors: Yoshiro Koda, Mikiko Soejima, Philip H Johnson, Elizabeth Smart, Hiroshi KimuraAbstract:Abstract The Bombay phenotype fails to express the ABH antigens of ABO blood group system on red blood cells and in secretions because of a lack in activities of the H gene ( FUT1 )- and Secretor gene ( FUT2 )-encoded α(1,2)fucosyltransferases. In this study, we have examined the FUT1 and the FUT2 from three unrelated Indian individuals with the Bombay phenotype. These three individuals were found to be homozygous for a T725G mutation in the coding region of the FUT1, which inactivated the enzyme activity. In addition, we did not detect any hybridized band corresponding to the FUT2 by Southern blot analysis using the catalytic domain of the FUT2 as a probe, indicating that the three individuals were homozygous for a gene deletion in the FUT2. These results suggest that the T725G mutation of FUT1 and the gene deletion of FUT2 are responsible for the classical Indian Bombay phenotype.
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structure and expression of h type gdp l fucose β d galactoside 2 α l fucosyltransferase gene FUT1 two transcription start sites and alternative splicing generate several forms of FUT1 mrna
Journal of Biological Chemistry, 1997Co-Authors: Yoshiro Koda, Mikiko Soejima, Hiroshi KimuraAbstract:Abstract The expression of the ABO antigens on erythrocyte membranes is regulated by H gene (FUT1)-encoded α(1,2)fucosyltransferase activity. We have examined the expression of the FUT1 in several tumor cell lines, including erythroid lineage and normal bone marrow cells, by Northern blot and/or reverse transcription-polymerase chain reaction (RT-PCR) analyses. RT-PCR indicated that bone marrow cells, erythroleukemic cells (HEL), and highly undifferentiated leukemic cells (K562) that have erythroid characteristics expressed the FUT1 mRNA while four leukemic cell lines did not. The FUT1 mRNA was also demonstrated in gastric, colonic, and ovarian (MCAS) cancer cell lines by RT-PCR. Northern blot analysis indicated that a 4.0-kilobase FUT1 transcript was expressed in some of these tumor cell lines. Rapid amplification of 5′ cDNA end (RACE) analysis suggested that the FUT1 transcript had several forms generated by two distinct transcription start sites and alternative splicing. The results of RT-PCR using specific primers for each starting exon suggested that two transcription initiation sites (exon 1A and exon 2A) of the FUT1 were identified in gastric cancer cells and in ovarian cancer cells. Only exon 1A was identified as a transcription start site in another gastric cancer cell line, two colonic cancer cell lines, and in K562 cells, whereas only exon 2A was identified in HEL cells and in bone marrow cells. These two transcription start sites were located 1.8 kilobases apart. Therefore, two distinct promoters appeared to be present in the FUT1 The distinct promoters of the FUT1 and alternative splicing of the FUT1 mRNA may be associated with time- and tissue-specific expression of the FUT1
