<i>FUT2</i> 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 his...
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doaj-6dbbcd2a2f434e7abf0fa1af17f192122020-11-25T03:54:57ZengMDPI AGPathogens2076-08172020-09-01979579510.3390/pathogens9100795<i>FUT2</i> Secretor Status Influences Susceptibility to VP4 Strain-Specific Rotavirus Infections in South African ChildrenJaime MacDonald0Michelle J. Groome1Janet Mans2Nicola Page3National Institute for Communicable Diseases, Sandringham 2131, South AfricaSouth African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg 2193, South AfricaDepartment of Medical Virology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South AfricaNational Institute for Communicable Diseases, Sandringham 2131, South AfricaGastroenteritis 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%; <i>p</i> < 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%; <i>p</i> = 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.https://www.mdpi.com/2076-0817/9/10/795rotavirussecretor statushisto-blood group antigensVP4 genotypes<i>FUT2</i>susceptibility |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jaime MacDonald Michelle J. Groome Janet Mans Nicola Page |
spellingShingle |
Jaime MacDonald Michelle J. Groome Janet Mans Nicola Page <i>FUT2</i> Secretor Status Influences Susceptibility to VP4 Strain-Specific Rotavirus Infections in South African Children Pathogens rotavirus secretor status histo-blood group antigens VP4 genotypes <i>FUT2</i> susceptibility |
author_facet |
Jaime MacDonald Michelle J. Groome Janet Mans Nicola Page |
author_sort |
Jaime MacDonald |
title |
<i>FUT2</i> Secretor Status Influences Susceptibility to VP4 Strain-Specific Rotavirus Infections in South African Children |
title_short |
<i>FUT2</i> Secretor Status Influences Susceptibility to VP4 Strain-Specific Rotavirus Infections in South African Children |
title_full |
<i>FUT2</i> Secretor Status Influences Susceptibility to VP4 Strain-Specific Rotavirus Infections in South African Children |
title_fullStr |
<i>FUT2</i> Secretor Status Influences Susceptibility to VP4 Strain-Specific Rotavirus Infections in South African Children |
title_full_unstemmed |
<i>FUT2</i> Secretor Status Influences Susceptibility to VP4 Strain-Specific Rotavirus Infections in South African Children |
title_sort |
<i>fut2</i> secretor status influences susceptibility to vp4 strain-specific rotavirus infections in south african children |
publisher |
MDPI AG |
series |
Pathogens |
issn |
2076-0817 |
publishDate |
2020-09-01 |
description |
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%; <i>p</i> < 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%; <i>p</i> = 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. |
topic |
rotavirus secretor status histo-blood group antigens VP4 genotypes <i>FUT2</i> susceptibility |
url |
https://www.mdpi.com/2076-0817/9/10/795 |
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