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巴基斯坦丙型肝炎病毒3a基因型包膜糖蛋白2的B细胞和T细胞表位的电子鉴定与保守性分析:迈向异源疫苗设计的一步

In Silico Identification and Conservation Analysis of B-cell and T-Cell Epitopes of Hepatitis C Virus 3a Genotype Enveloped Glycoprotein 2 From Pakistan: A Step Towards Heterologous Vaccine Design.

作者信息

Ikram Aqsa, Anjum Sadia, Tahir Muhammad

机构信息

Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.

出版信息

Hepat Mon. 2014 Jun 1;14(6):e9832. doi: 10.5812/hepatmon.9832. eCollection 2014 Jun.

Abstract

BACKGROUND

Hepatitis C virus (HCV) is known for the eminent global disease burden responsible for encumbering public health. Development of an effective vaccine is the major need of the day; however, several obstacles loom ahead of this objective. One of the major barriers is that as a RNA virus, it mutates rapidly resulting in high sequence divergence and several viral isolates in the world. Theglycoprotein 2 (gpE2) is the primary component of HCV envelope with direct interaction with the host cell surface receptors; it is an indispensable target of neutralizing antibodies and hence, should be a fundamental component of vaccine design.

OBJECTIVES

This study focused on B-cells and T-cells epitopes prediction in HCV gpE2, particularly in 3a genotype, in Pakistan and identification of the conserved epitopes among various 3a isolates at global level, principally conserved across HCV major genotypes.

MATERIALS AND METHODS

Epitope finding was done by using online available bioinformatics tools including Immune Epitope Database (IEDB), ProPred-I, and ProPred. Conservation of these epitopes was found by aligning selected gpE2 sequences using MultAlin online software and conservancy analysis tool available at IEDB.

RESULTS

Many B-cell and T-cell epitopes predicted in gpE2 were found conserved among HCV 3a genotypes whereas few were conserved in other genotypes anticipating these epitopes as potential candidates of producing strong B-cell and T-cell response against HCV 3a and other genotypes.

CONCLUSIONS

HCV gpE2 is an ideal target for HCV vaccine. Prediction of epitope immunogenicity and characterization on the basis of peptide sequences will be significantly helpful for development of a heterologous vaccine against HCV variants.

摘要

背景

丙型肝炎病毒(HCV)因给全球公共卫生带来巨大疾病负担而闻名。开发一种有效的疫苗是当务之急;然而,这一目标面临诸多障碍。主要障碍之一是,作为一种RNA病毒,它变异迅速,导致世界上存在高度的序列差异和多种病毒分离株。糖蛋白2(gpE2)是HCV包膜的主要成分,与宿主细胞表面受体直接相互作用;它是中和抗体的不可或缺的靶点,因此应是疫苗设计的基本组成部分。

目的

本研究聚焦于巴基斯坦HCV gpE2中B细胞和T细胞表位的预测,特别是3a基因型,并在全球层面鉴定各种3a分离株之间的保守表位,主要是在HCV主要基因型中保守的表位。

材料与方法

通过使用在线可用的生物信息学工具进行表位查找,包括免疫表位数据库(IEDB)、ProPred-I和ProPred。通过使用MultAlin在线软件和IEDB提供的保守性分析工具对选定的gpE2序列进行比对,发现这些表位的保守性。

结果

在gpE2中预测的许多B细胞和T细胞表位在HCV 3a基因型中是保守的,而在其他基因型中只有少数是保守的,预计这些表位是产生针对HCV 3a和其他基因型的强烈B细胞和T细胞反应的潜在候选者。

结论

HCV gpE2是HCV疫苗的理想靶点。基于肽序列预测表位免疫原性并进行表征将对开发针对HCV变体的异源疫苗有显著帮助。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8639/4071360/06536e31a85a/hepatmon-14-06-9832-i001.jpg

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