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丙型肝炎病毒4型的异质性与新抗原表位

Heterogeneity and new epitopes of hepatitis C virus genotype 4.

作者信息

Omran Moataza H, Nabil Wael, Youssef Samar S, El-Sayed Mervat, El Awady Mostafa K

机构信息

Microbial Biotechnology Department, Genetic Engineering Division, National Research Centre, Dokki Cairo, Egypt.

出版信息

Hepat Mon. 2013 Aug 1;13(8):e10521. doi: 10.5812/hepatmon.10521. eCollection 2013.

Abstract

BACKGROUND

Hepatitis C virus (HCV) was found to have a major role in human liver disease by its ability to face the host-cell defenses and the immune system. Heterogeneity of HCV was the key for its adaptation to its host and represented a significant hurdle for the development of both effective vaccines as well as for novel therapeutic interventions.

OBJECTIVES

Due to the heterogeneity of HCV virus because of both high replication and high mutation rate in vivo, this study was conducted to analyze different isolates of Egyptian patients of genotype 4, of the most mutant regions of the virus (E1 and E2) as they played an important role in viral persistence by escaping from the immune system of the host body.

PATIENTS AND METHODS

This study was conducted through PCR amplification of E1 and E2 regions, sequencing and phylogenetic analysis, calculating synonyms and non-synonyms substitutions, finding the possible glycosylation sites and different epitope domains.

RESULTS

The present work figured out that the heterogeneity of the quasispecies of our local strains 4a was high showing up 15% diversity. This study also showed four glycosylation sites that play an important role in the entry of the virus and protein folding. Besides, different epitpoes were identified in different regions of the E1 and E2 domains; a finding which would help in determining the neutralizing and non- neutralizing antibodies.

CONCLUSIONS

This study would help in understanding the driving forces of genetic diversity and would be fundamental for representing potential candidate targets for antibodies and the development of vaccine trials.

摘要

背景

丙型肝炎病毒(HCV)因其应对宿主细胞防御和免疫系统的能力,被发现是人类肝脏疾病的主要致病因素。HCV的异质性是其适应宿主的关键,也是开发有效疫苗和新型治疗干预措施的重大障碍。

目的

由于HCV在体内具有高复制率和高突变率,导致病毒具有异质性,本研究旨在分析埃及4型患者病毒不同分离株中病毒最易突变区域(E1和E2)的情况,因为这些区域通过逃避宿主机体免疫系统在病毒持续存在中发挥重要作用。

患者和方法

本研究通过对E1和E2区域进行PCR扩增、测序和系统发育分析,计算同义替换和非同义替换,寻找可能的糖基化位点和不同的表位域。

结果

目前的研究表明,我们本地4a型毒株准种的异质性很高,多样性达15%。本研究还发现了四个在病毒进入和蛋白质折叠中起重要作用的糖基化位点。此外,在E1和E2结构域的不同区域鉴定出了不同的表位;这一发现将有助于确定中和抗体和非中和抗体。

结论

本研究将有助于理解遗传多样性的驱动因素,并为确定抗体的潜在候选靶点和开展疫苗试验奠定基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b30/3796197/835ffa8006b1/hepatmon-13-08-10521-i001.jpg

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