Rotavirus A shedding and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil, 2014\u20132018

Carina Pacheco Cantelli,José Paulo Gagliardi Leite,Rosane Maria Santos De Assis,José Júnior Barros,Marize Pereira Miagostovich,Lennart Svensson,Alvaro Jorge Velloso,Johan Nordgren,Francisco Campello Do Amaral Mello,Patricia Brasil,Denise Cotrim Da Cunha,Marcia Terezinha Baroni De Moraes

doi:10.1038/s41598-020-64025-0

Carina Pacheco Cantelli, José Paulo Gagliardi Leite + Show 10 more

Open Access

https://doi.org/10.1038/s41598-020-64025-0

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Abstract

Recent studies have investigated whether the human histo-blood group antigen (HBGAs) could affect the effectiveness of the oral rotavirus vaccines, suggesting secretor positive individuals develop a more robust response. We investigated the Rotavirus A (RVA) shedding in association with the host susceptibility profile in children from a birth community-cohort in Rio de Janeiro, Brazil, from 2014 to 2018. A total of 132 children were followed-up between 0 to 11-month-old, stool samples were collected before/after the 1st/2nd RV1 vaccination doses and saliva samples were collected during the study. RVA shedding was screened by RT-qPCR and G/P genotypes determined by multiplex RT-PCR and/or Sanger nucleotide sequencing. The sequencing indicated an F167L amino acid change in the RV1 VP8* P[8] in 20.5% of shedding follow-ups and these mutant subpopulations were quantified by pyrosequencing. The HBGA/secretor status was determined and 80.3% of the children were secretors. Twenty-one FUT2 gene SNPs were identified and two new mutations were observed. The mutant F167L RV1 VP8* P[8] was detected significantly more in Le (a+b+) secretors (90.5%) compared to non-secretors and even to secretors Le (a−b+) (9.5%). The study highlights the probable association between RV1 shedding and HBGAs as a marker for evaluating vaccine strain host susceptibility.

Highlights

A rotaviruses (RVA) diarrhea has decreased substantially, with reductions in hospitalizations and deaths in many countries, including Brazil2–6
Studies involving the histo-blood group antigens (HBGA) have shown the importance of the VP8* domain; in the early stages of the pathogenesis of RVA infection11–13 as well as identifying RV1 G1P[8] shedding by nucleotide sequencing14,15
A total of 19.2% (109/569) of stool specimens were positive for RVA by one-step reverse transcription-quantitative polymerase chain reaction (RT-qPCR), corresponding to 62.1% (82/132) of all children enrolled in this prospective study

Summary

Introduction

A rotaviruses (RVA) diarrhea has decreased substantially, with reductions in hospitalizations and deaths in many countries, including Brazil. HBGAs are complex glycans (type 1 H, Lea, Leb) present on cell surfaces and in biological fluids, such as blood, breast milk, saliva, and intestinal mucosa. HBGAs are complex glycans (type 1 H, Lea, Leb) present on cell surfaces and in biological fluids, such as blood, breast milk, saliva, and intestinal mucosa16 These glycans are catalyzed by glycosyltransferases, through sequential addition of monossaccharides to an initial precursor; these transferases are encoded by the AB0, FUT2 (Secretor) and FUT3 (Lewis) genes. Secretor status is a host susceptibility factor in several infectious diseases, such as viral gastroenteritis by some RVA and noroviruses genotypes, and gastritis-ulcers by H. The HBGA genes’ mutations distributed worldwide as single nucleotide polymorphisms (SNPs) work as identity markers favoring certain conditions of susceptibility or resistance to infections or disorders

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