A FUT2 Gene Common Polymorphism Determines Resistance to Rotavirus A of the P[8] Genotype

Imbert-Marcille, Berthe-Marie; Barbé, Laure; Dupé, Mathilde; Moullac-Vaidye, Béatrice Le; Besse, Bernard; Peltier, Cécile; Ruvoën-Clouet, Nathalie; Pendu, Jacques Le

doi:10.1093/infdis/jit655

Cited by 139 publications

(127 citation statements)

References 12 publications

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“…The ligand binding clefts in P [4], P [8], and P [19] VP8* are ϳ0.5 Å wider than those in P [3] and P [14] VP8* proteins. The distance between the C␣ atoms of Pro157 and Thr186 in P [3] is ϳ10.7 Å, and that of Thr157 and Thr186 in P [19] VP8* is ϳ11.2 Å. Residue 135 of P [3] and P [14] (Fig. 4B, thin arrow), which was deleted in P [4], P [8], and P [19] (Fig.…”

Section: Detection Of P[19] Vp8* Attachment To Synthetic Oligosaccharmentioning

confidence: 81%

“…P [19] VP8* has a cleft that separates the two ␤-barrel sheets (Fig. 4B, thick arrows) wider than those of P [14] (PDB accession no. 2DWR) and animal P [3] (PDB accession no.…”

Section: Detection Of P[19] Vp8* Attachment To Synthetic Oligosaccharmentioning

confidence: 99%

“…P [11] showed obvious binding to type 1/type 2 precursors (16,17). In addition, P [9], P [14], and P [25] all bound to A type HBGA (A-HBGA) (18). Using saturation transfer difference nuclear magnetic resonance (STD-NMR), DS-1 P [4], RV-3 P [6], ST-3 P [6], and HAL1141 P [14] RVs were shown to bind to A-HBGA, whereas Wa P [8] did not (19).…”

mentioning

confidence: 94%

“…Previous studies by oligosaccharide and saliva binding assays showed that P [4] and P [8] bound to Lewis b (Le b ) and H1, while P [6] recognized only H1 (11,14,15). P [11] showed obvious binding to type 1/type 2 precursors (16,17).…”

mentioning

confidence: 95%

“…In addition, P [9], P [14], and P [25] all bound to A type HBGA (A-HBGA) (18). Using saturation transfer difference nuclear magnetic resonance (STD-NMR), DS-1 P [4], RV-3 P [6], ST-3 P [6], and HAL1141 P [14] RVs were shown to bind to A-HBGA, whereas Wa P [8] did not (19). In addition, the VP8* protein of Wa also showed no binding to H1 or [6], and P [8]) are all clustered in P [II].…”

mentioning

confidence: 99%

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

Sun

Peng

et al. 2016

J Virol

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Rotaviruses (RVsR otaviruses (RVs) are the major causative agents of acute gastroenteritis in young children and animals worldwide (1). The RV genome contains 11 segments of double-stranded RNA encoding 12 proteins: six structural proteins (VP1, VP2, VP3, VP4, VP6, and VP7) and six nonstructural proteins (NSP1 to NSP6) (2). RVs are classified into 8 species (A to H) by the antigenicity of the VP6 protein (3). Group A rotavirus (RVA) is a major cause of human RV-associated gastroenteritis (4). RVA can be classified into various G and P types on the basis of glycoprotein VP7 and protease-sensitive VP4, respectively. To date, at least 27 G and 35 P genotypes have been reported (5). The fact that the segmented genome undergoes point mutations, reassortment, and gene rearrangements accounts for the large genetic diversity of RVs (1).VP4 can be cleaved by protease to yield N-terminal VP8* and C-terminal VP5* (6). VP8* includes the VP4 spike head and is reported to bind to cell surface glycans essential for cell invasion (7). The ability of a virus to invade host cells is crucial for its replication, host tropism, and pathogenicity. Notably, VP8* is the most variable domain. VP8* proteins of sialidase-sensitive RVs were reported to interact with sialic acids (Sia) (8); however, most animal RVs and almost all human RVs were sialidase insensitive (9). It was noted that many of the sialidase-insensitive RVA strains interact with Sia at subterminal sites of glycoprotein receptors (10). Recently, histo-blood group antigens (HBGAs) have been reported to be attachment factors for human RVs by interacting with VP8* (11,12). HBGAs are a group of carbohydrates present on the surfaces of red blood cells and mucosal epithelia and as free oligosaccharides in saliva, blood, and milk (13).Previous studies by oligosaccharide and saliva binding assays showed that P

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Section: Detection Of P[19] Vp8* Attachment To Synthetic Oligosaccharmentioning

confidence: 81%

“…P [19] VP8* has a cleft that separates the two ␤-barrel sheets (Fig. 4B, thick arrows) wider than those of P [14] (PDB accession no. 2DWR) and animal P [3] (PDB accession no.…”

Section: Detection Of P[19] Vp8* Attachment To Synthetic Oligosaccharmentioning

confidence: 99%

mentioning

confidence: 94%

mentioning

confidence: 95%

mentioning

confidence: 99%

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

Sun

Peng

et al. 2016

J Virol

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Epidemiologic Association BetweenFUT2Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States

et al. 2015

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IMPORTANCE A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus.OBJECTIVE We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. DESIGN, SETTING, AND PARTICIPANTSMulticenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013. MAIN OUTCOMES AND MEASURESPaired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test-positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis.RESULTS One (0.5%) of 189 rotavirus test-positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%-100%]) against severe rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCESevere rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower prevalence of nonsecretors among Hispanic children may translate to an enhanced burden of rotavirus gastroenteritis among this group. Our findings may have bearing on our full understanding of rotavirus infections and the effects of vaccination in diverse populations.

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High‐resolution melting analysis for detection of fusion allele of FUT2

Soejima

Koda

2020

Electrophoresis

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The secretor status of ABH antigens, determined by FUT2 polymorphisms, affects susceptibility to various infectious diseases. In addition to many SNPs responsible for the nonsecretor phenotype, five nonfunctional alleles (se) resulting from copy number variations have been reported. One of the five alleles generated by an unequal crossover between FUT2 and a pseudogene (SEC1), is sefus. This allele may be misidentified as a functional allele if only common inactivating SNPs are genotyped because it contains the 3ʹ region of the functional FUT2. Therefore, accurate detection of sefus is desirable. For this purpose, a high‐resolution melting (HRM) analysis is developed for detection of sefus in which a 284bp fragment of SEC1 and sefus but not FUT2, are amplified. This HRM analysis detected sefus reliably. Thus, an initial screening or prescreening for sefus using HRM analysis seems to be useful for association studies of FUT2.

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A FUT2 Gene Common Polymorphism Determines Resistance to Rotavirus A of the P[8] Genotype

Cited by 139 publications

References 12 publications

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

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

Epidemiologic Association BetweenFUT2Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States

High‐resolution melting analysis for detection of fusion allele of FUT2

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