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巴西疫苗引入后时代严重腹泻患儿中 G1P[8]轮状病毒:抗原 VP7 和 VP4 区基因重配和结构修饰的证据。

G1P[8] Rotavirus in children with severe diarrhea in the post-vaccine introduction era in Brazil: Evidence of reassortments and structural modifications of the antigenic VP7 and VP4 regions.

机构信息

Programa de Pós Graduação em Biologia Parasitária da Amazônia, Universidade do Estado do Pará, Instituto Evandro Chagas, Brazil; Programa de Pós Graduação em Virologia do Instituto Evandro Chagas, Brazil.

Programa de Pós Graduação em Virologia do Instituto Evandro Chagas, Brazil; Instituto Evandro Chagas, Secretaria de Vigilância em Saúde, Ministério da Saúde, Brazil.

出版信息

Infect Genet Evol. 2019 Apr;69:255-266. doi: 10.1016/j.meegid.2019.02.009. Epub 2019 Feb 11.

Abstract

Worldwide rotaviruses A (RVA) are responsible for approximately 215,000 deaths annually among children aged <5 years. RVA G1P[8] remains associated with >50% of gastroenteritis cases in this age group. The aim of this study was to assess the genetic variability of G1P[8] strains detected in children with severe diarrhea in Belém, Pará, Brazil, during the post-rotavirus vaccine introduction era. Phylogenetic analysis clustered the VP4 and VP7 genes of 40 samples selected between 2009 and 2011 into lineages found to be different from the Rotarix® vaccine strain. A detailed investigation of their complete genotype constellations identified 2 reassortant viruses (5%), resulting from reassortments between the genogroups Wa-like and DS-1-like (G1-P[8]-I1-R2-C1-M1-A1-N1-T2-E1-H1) and Wa-like and AU-1-like (G1-P[8]-I1-R3-C1-M1-A1-N1-T1-E1-H1) genotype constellations. A comparison of the amino acid residues presents in the antigenic epitopes of VP7 and VP4, showed differences in the electrostatic charges distribution, between wild type Brazilian strains and the Rotarix® and RotaTeq® vaccine strains. These findings reflect the structural analyses of the antigenic regions of VP7 and VP4 of the RVA G1P[8] in children with gastroenteritis in Northern Brazil raising the hypothesis that structural modifications at these sites over time may account for the emergence of new strains that could possibly pose a challenge to current vaccines.

摘要

在轮状病毒疫苗问世后,全世界 A 型轮状病毒(RVA)每年仍导致 5 岁以下儿童死亡约 21.5 万例。在该年龄组中,G1P[8]型轮状病毒仍然与超过 50%的胃肠炎病例有关。本研究旨在评估巴西帕拉州贝伦地区患有严重腹泻的儿童中检测到的 G1P[8]型 RVA 株的遗传变异性。系统进化分析将 2009 年至 2011 年间选择的 40 个样本的 VP4 和 VP7 基因聚类为与 Rotarix®疫苗株不同的谱系。对其完整基因型结构的详细调查确定了 2 种重组病毒(5%),它们是由 Wa 样和 DS-1 样(G1-P[8]-I1-R2-C1-M1-A1-N1-T2-E1-H1)和 Wa 样和 AU-1 样(G1-P[8]-I1-R3-C1-M1-A1-N1-T1-E1-H1)基因群之间的重组产生的。对 VP7 和 VP4 抗原表位中存在的氨基酸残基进行比较,显示巴西野生株与 Rotarix®和 RotaTeq®疫苗株在电荷分布上存在差异。这些发现反映了巴西北部地区胃肠炎患儿中 RVA G1P[8]的 VP7 和 VP4 抗原区的结构分析,提出了随着时间的推移,这些部位的结构修饰可能是新出现的菌株的原因,这些新出现的菌株可能对当前疫苗构成挑战。

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