MacDonald, Jaime ClaireGroome, Michelle J.Janet, JanetPage, Nicola Anne2020-12-282020-12-282020-09MacDonald, J., Groome, M.J., Mans, J. et al. 2020, 'FUT2 secretor status influences susceptibility to VP4 strain-specific rotavirus infections in South African children', Pathogens, vol. 9, no. 10, art. 795, pp. 1-9.2076-0817 (online)10.3390/pathogens9100795http://hdl.handle.net/2263/77503Supplementary Material : File: Final DBS Cohort Results_7.9.2020.Gastroenteritis is a preventable cause of morbidity and mortality worldwide. Rotavirus vaccination has significantly reduced the disease burden, but the sub-optimal vaccine efficacy observed in low-income regions needs improvement. Rotavirus VP4 ‘spike’ proteins interact with FUT2-defined, human histo-blood group antigens on mucosal surfaces, potentially influencing strain circulation and the efficacy of P[8]-based rotavirus vaccines. Secretor status was investigated in 500 children <5 years-old hospitalised with diarrhoea, including 250 previously genotyped rotavirus-positive cases (P[8] = 124, P[4] = 86, and P[6] = 40), and 250 rotavirus-negative controls. Secretor status genotyping detected the globally prevalent G428A single nucleotide polymorphism (SNP) and was confirmed by Sanger sequencing in 10% of participants. The proportions of secretors in rotavirus-positive cases (74%) were significantly higher than in the rotavirus-negative controls (58%; p < 0.001). The rotavirus genotypes P[8] and P[4] were observed at significantly higher proportions in secretors (78%) than in non-secretors (22%), contrasting with P[6] genotypes with similar proportions amongst secretors (53%) and non-secretors (47%; p = 0.001). This suggests that rotavirus interacts with secretors and non-secretors in a VP4 strain-specific manner; thus, secretor status may partially influence rotavirus VP4 wild-type circulation and P[8] rotavirus vaccine efficacy. The study detected a mutation (rs1800025) ~50 bp downstream of the G428A SNP that would overestimate non-secretors in African populations when using the TaqMan®SNP Genotyping Assay.en© 2020 by the authors. Licensee: MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).RotavirusSecretor statusHisto-blood group antigensVP4 genotypesFUT2SusceptibilityVaccinesArticle