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加纳献血者体内丙型肝炎病毒的核心编码序列主要是不同 2 型株的嵌合体,无法区分亚型。

Core encoding sequences of Hepatitis C virus in Ghanaian blood donors are predominantly mosaics of different genotype 2 strains and cannot distinguish subtypes.

机构信息

Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, Accra, Ghana.

Department of Biochemistry, Cell and Molecular Biology, School of Biological Sciences, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana.

出版信息

BMC Infect Dis. 2019 Jun 17;19(1):533. doi: 10.1186/s12879-019-4155-4.

Abstract

BACKGROUND

Distribution of Hepatitis C virus (HCV) genotypes varies significantly worldwide. Genomic diversity between genotypes has implications for treatment, vaccine development and optimal design of HCV diagnostic assays. Molecular characterization of HCV in different geographical areas is therefore very essential for management and public health control of HCV infection. This study investigated the molecular epidemiology and characteristics of HCV genotypes in healthy individuals in Accra, Ghana.

METHODS

An experimental study was carried out on blood samples obtained from voluntary blood donors. Two hundred samples were initially screened for HCV antibodies and infection was confirmed by RNA detection through RT-PCR of the 5'-untranslated region (5'UTR). The core gene sequences were analysed for HCV genotype determination by genotype-specific PCR; and then by cloning and direct sequencing followed by phylogenetic analysis. The sequences were further analysed in detail by similarity plotting.

RESULTS

Molecular diagnosis confirmed the presence of HCV RNA in 2 out of 200 (1%) blood donors. Initial genotyping by genotype-specific PCR identified all two infections as subtypes 2a and 2b of genotype 2. Extensive evolutionary and genetic analyses indicated two epidemiological profiles. First, phylogenetic tree topologies clearly showed that, collectively, the core sequences of the Ghanaian HCV isolates belong to a single, distinct genetic group within HCV genotype 2 cluster, with high genetic similarity and rapid sequence variation in a single individual. Second, the sequences are mosaics comprising 2e and other genotype 2 subtype fragments. The analyses underscore a unique and complex HCV genotype 2 core sequence profile of the Ghanaian isolates.

CONCLUSIONS

Analysis of HCV core encoding sequences from Ghanaian blood donors in Accra confirmed predominance of genotype 2 HCV among healthy individuals. However, the isolates could not be classified into subtypes, possibly due to their complex sequence pattern that might suggest high mutability of the prevailing genotype. The core region of Ghanaian HCV therefore may not be suitable for distinguishing subtypes. These findings extend those from previous studies and thus underscore the need to search for subtype-informative region of Ghanaian HCV to elucidate the genetic diversity and factors determining outcome of HCV infections in Ghana.

摘要

背景

丙型肝炎病毒(HCV)基因型在全球范围内分布差异显著。基因型之间的基因组多样性对治疗、疫苗开发和 HCV 诊断检测的最佳设计具有影响。因此,对不同地理区域 HCV 的分子特征进行描述对于 HCV 感染的管理和公共卫生控制非常重要。本研究调查了加纳阿克拉地区健康个体中 HCV 基因型的分子流行病学和特征。

方法

对来自自愿献血者的血液样本进行了一项实验研究。最初筛选了 200 个样本以检测 HCV 抗体,并用 RT-PCR 检测 5'-非翻译区(5'UTR)来确认 RNA 感染。通过基因型特异性 PCR 分析核心基因序列以确定 HCV 基因型;然后通过克隆和直接测序以及系统发生分析进行确定。进一步通过相似性绘图对序列进行详细分析。

结果

分子诊断证实,在 200 名献血者中有 2 人(1%)存在 HCV RNA。通过基因型特异性 PCR 进行的初步基因分型鉴定,这两种感染均为基因型 2 的 2a 和 2b 亚型。广泛的进化和遗传分析表明存在两种流行病学特征。首先,系统发生树拓扑结构清楚地表明,加纳 HCV 分离株的核心序列共同属于 HCV 基因型 2 簇内的一个单一、独特的遗传群,具有高度的遗传相似性和个体内快速的序列变异。其次,序列是由 2e 和其他基因型 2 亚型片段组成的嵌合体。分析强调了加纳 HCV 基因型 2 核心序列的独特而复杂的特征。

结论

对加纳阿克拉地区健康献血者的 HCV 核心编码序列进行分析,证实了 HCV 基因型 2 在健康个体中占主导地位。然而,这些分离株不能被分类为亚型,可能是由于其复杂的序列模式,这可能表明主要流行基因型的高突变性。因此,加纳 HCV 的核心区域可能不适合用于区分亚型。这些发现扩展了以前的研究结果,因此需要寻找加纳 HCV 的亚型信息区域,以阐明加纳 HCV 感染的遗传多样性和决定因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c21d/6580569/de13b22eac45/12879_2019_4155_Fig1_HTML.jpg

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