FUT2 Secretor Status Influences Susceptibility to VP4 Strain-Specific Rotavirus Infections in South African Children

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.