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沙特阿拉伯患者中丙型肝炎病毒1a和4a亚型分离株的病毒学监测、分子系统发育及进化动力学

Virological surveillance, molecular phylogeny, and evolutionary dynamics of hepatitis C virus subtypes 1a and 4a isolates in patients from Saudi Arabia.

作者信息

AlMalki Waleed H, Shahid Imran, Abdalla Ashraf N, Johargy Ayman K, Ahmed Muhammad, Hassan Sajida

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, Umm-Al-Qura University, Al-abidiyah, P.O. Box 13578, Makkah 21955, Saudi Arabia.

Department of Pharmacology and Toxicology, Faculty of Medicine, Umm-Al-Qura University, Al-abidiyah, P.O. Box 13578, Makkah 21955, Saudi Arabia.

出版信息

Saudi J Biol Sci. 2021 Mar;28(3):1664-1677. doi: 10.1016/j.sjbs.2020.11.089. Epub 2020 Dec 8.

DOI:10.1016/j.sjbs.2020.11.089
PMID:33732052
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7938134/
Abstract

Hepatitis C virus (HCV) subtypes are pre-requisite to predict endemicity, epidemiology, clinical pathogenesis, diagnosis, and treatment of chronic hepatitis C infection. HCV genotypes 4 and 1 are the most prevalent in Saudi Arabia, however; less consensus data exist on circulating HCV subtypes in infected individuals. This study was aimed to demonstrate the virological surveillance, phylogenetic analysis, and evolutionary relationship of HCV genotypes 4 and 1 subtypes in the Saudi population with the rest of the world. Fifty-five clinical specimens from different parts of the country were analyzed based on 5' untranslated region (5' UTR) amplification, direct sequencing, and for molecular evolutionary genetic analysis. Pair-wise comparison and multiple sequence alignment were performed to determine the nucleotide conservation, nucleotide variation, and positional mutations within the sequenced isolates. The evolutionary relationship of sequenced HCV isolates with referenced HCV strains from the rest of the world was established by computing pairwise genetic distances and generating phylogenetic trees. Twelve new sequences were submitted to GenBank, NCBI database. The results revealed that HCV subtype 4a is more prevalent preceded by 1a in the Saudi population. Molecular phylogeny predicts the descendants' relationship of subtype 4a isolates very close to Egyptian prototype HCV strains, while 1a isolates were homogeneous and clustering to the European and North American genetic lineages. The implications of this study highlight the importance of HCV subtyping as an indispensable tool to monitor the distribution of viral strains, to determine the risk factors of infection prevalence, and to investigate clinical differences of treatment outcomes among intergenotypic and intragenotypic isolates in the treated population.

摘要

丙型肝炎病毒(HCV)亚型是预测慢性丙型肝炎感染的地方性、流行病学、临床发病机制、诊断和治疗的先决条件。然而,HCV基因4型和1型在沙特阿拉伯最为普遍;关于受感染个体中循环HCV亚型的共识数据较少。本研究旨在证明沙特人群中HCV基因4型和1型亚型与世界其他地区的病毒学监测、系统发育分析和进化关系。基于5'非翻译区(5'UTR)扩增、直接测序以及分子进化遗传分析,对来自该国不同地区的55份临床标本进行了分析。进行成对比较和多序列比对以确定测序分离株中的核苷酸保守性、核苷酸变异和位置突变。通过计算成对遗传距离和生成系统发育树,建立了测序的HCV分离株与来自世界其他地区的参考HCV毒株的进化关系。12条新序列已提交至NCBI数据库GenBank。结果显示,在沙特人群中,HCV 4a亚型比1a亚型更普遍。分子系统发育预测4a亚型分离株的后代关系与埃及原型HCV毒株非常接近,而1a分离株是同质的,聚类到欧洲和北美遗传谱系。本研究的意义突出了HCV基因分型作为监测病毒株分布、确定感染流行风险因素以及研究治疗人群中基因间和基因内分离株治疗结果临床差异的不可或缺工具的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f547/7938134/7d274fd85541/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f547/7938134/2e6ba0f77ec4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f547/7938134/0ef958a031a5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f547/7938134/c9b720170ca5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f547/7938134/ba0a7ca01b08/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f547/7938134/7d274fd85541/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f547/7938134/2e6ba0f77ec4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f547/7938134/0ef958a031a5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f547/7938134/c9b720170ca5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f547/7938134/ba0a7ca01b08/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f547/7938134/7d274fd85541/gr5.jpg

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Developments in the treatment of HCV genotype 3 infection.丙型肝炎病毒基因型 3 感染治疗的进展。
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