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印度尼西亚急性胃肠炎患儿中流行的轮状病毒株 VP4、VP7 和 NSP4 基因的系统进化和免疫信息学分析。

Phylogenetic and immunoinformatic analysis of VP4, VP7, and NSP4 genes of rotavirus strains circulating in children with acute gastroenteritis in Indonesia.

机构信息

Department of Microbiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

Department of Microbiology, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia.

出版信息

J Med Virol. 2019 Oct;91(10):1776-1787. doi: 10.1002/jmv.25527. Epub 2019 Jul 11.

Abstract

Rotavirus is a major cause of diarrhea in Indonesian children. However, rotavirus vaccines have not been introduced in the national immunization program of Indonesia. Understanding the genetic diversity and conserved antigenic regions of circulating strains are therefore essential to assess the potential efficacy of rotavirus vaccines. We collected fecal samples from hospitalized children less than 5 years of age with acute diarrhea. Rotavirus genotyping was performed by reverse transcriptase polymerase chain reaction, followed by sequencing of the VP4, VP7, and NSP4 genes of representative strains. Phylogenetic analysis was performed to investigate their relationship with globally circulating strains. Conservational analysis, immunoinformatics, and epitope mapping in comparison to vaccine strains were also performed. The sequence analyses showed that differences of multiple amino acid residues existed between the VP4, VP7, and NSP4 antigenic regions of the vaccine strains and the Indonesian isolates. However, many predicted conserved epitopes with higher antigenicity were observed in the vaccine and Indonesian strains, conferring the importance of these epitopes. The identified epitopes showed a higher potential of rotavirus vaccine to be employed in Indonesia. It could also be helpful to inform the design of a peptide vaccine based on the conserved regions and epitopes in the viral proteins.

摘要

轮状病毒是印度尼西亚儿童腹泻的主要原因。然而,轮状病毒疫苗尚未被纳入印度尼西亚的国家免疫计划。因此,了解循环毒株的遗传多样性和保守抗原区域对于评估轮状病毒疫苗的潜在效果至关重要。我们收集了住院的 5 岁以下急性腹泻儿童的粪便样本。通过逆转录聚合酶链反应(RT-PCR)进行轮状病毒基因分型,随后对代表性毒株的 VP4、VP7 和 NSP4 基因进行测序。通过系统进化分析来研究它们与全球流行株的关系。还进行了保守性分析、免疫信息学分析和与疫苗株的表位作图分析。序列分析表明,疫苗株和印度尼西亚分离株的 VP4、VP7 和 NSP4 抗原区域存在多个氨基酸残基的差异。然而,在疫苗株和印度尼西亚分离株中观察到许多具有更高抗原性的预测保守表位,这些表位非常重要。所鉴定的表位表明,轮状病毒疫苗在印度尼西亚具有更高的应用潜力。这些表位也有助于基于病毒蛋白的保守区域和表位来设计基于肽的疫苗。

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