Molecular Biology Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
Virology Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
J Med Virol. 2016 Aug;88(8):1376-83. doi: 10.1002/jmv.24470. Epub 2016 Feb 12.
Intravenous drug users (IDUs) represent a highly-infected reservoir for Hepatitis C virus (HCV) worldwide, harboring some of the most elevated prevalences and majority of the epidemic in developed nations. Studies aimed at sequencing regions of the viral genome uncovered amino acid mutations, some of which have been implicated in resistance to standard of care pegylated interferon/Ribavirin double therapy. Using the nested PCR method on the Core region of HCV strains in Moroccan IDUs living in the Tangier region this study sought to identify genotype-specific amino acid mutations, followed by Phylogenetic methods in order to compare them with international strains so as to identify sequences of highest homology. Genotyping was confirmed and recombination events excluded by line-probe assay. Italy was found most homologous for genotypes 1a and 3a, Iran for genotype 1a and Egypt for genotype 4a. Amino Acid Mutation analysis revealed the following novel genotype 3a-specific mutations: N16I, L36V, T49A, P71S, T75S, and T110N. The outcome of this work describes the HCV genetic heterogeneity in high-risk intravenous drug users, and it gives clues to the global migratory flow of genotypes as they cross geographical boundaries between various IDU populations and identifies "signature" amino acid mutations traceable to HCV genotype 3a. Identification of key amino acid positions in the HCV Core region with higher rates of mutations paves the way for eventual clinical trials seeking to establish a link between these recurrent mutations and response to standard of care Interferon and Ribavirin antiviral therapy. J. Med. Virol. 88:1376-1383, 2016. © 2016 Wiley Periodicals, Inc.
静脉药物使用者(IDUs)在全球范围内代表了丙型肝炎病毒(HCV)的高度感染储存库,在发达国家拥有一些最高的流行率和大多数流行。旨在对病毒基因组区域进行测序的研究揭示了氨基酸突变,其中一些与对标准护理聚乙二醇干扰素/利巴韦林双重治疗的耐药性有关。本研究使用嵌套 PCR 方法对生活在丹吉尔地区的摩洛哥 IDUs 中的 HCV 株的核心区域进行了研究,旨在确定基因型特异性氨基酸突变,然后进行系统发育方法,以便将其与国际株进行比较,以确定同源性最高的序列。通过线探针分析确认基因分型并排除重组事件。意大利与基因型 1a 和 3a 最为相似,伊朗与基因型 1a 最为相似,埃及与基因型 4a 最为相似。氨基酸突变分析显示了以下新型基因型 3a 特异性突变:N16I、L36V、T49A、P71S、T75S 和 T110N。这项工作的结果描述了高危静脉药物使用者中 HCV 的遗传异质性,并为跨越不同 IDU 人群之间的地理边界的基因型的全球迁移流动提供了线索,并确定了可追踪 HCV 基因型 3a 的“特征”氨基酸突变。鉴定 HCV 核心区域中具有较高突变率的关键氨基酸位置为最终临床试验铺平了道路,这些临床试验旨在确定这些反复出现的突变与标准护理干扰素和利巴韦林抗病毒治疗之间的关系。J. Med. Virol. 88:1376-1383, 2016. © 2016 Wiley Periodicals, Inc.