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德国一名 HIV-1 合并感染个体中分离出的 HCV 基因 1 型 divergent 株的特征,该株被归为一个新的 1o 亚型。

Characterization of a hepatitis C virus genotype 1 divergent isolate from an HIV-1 coinfected individual in Germany assigned to a new subtype 1o.

机构信息

Division of Viral Gastroenteritis, Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, 13353, Berlin, Germany.

Division of HIV and other Retroviruses, Department of Infectious Diseases, Robert Koch Institute, 13353, Berlin, Germany.

出版信息

Virol J. 2019 Mar 4;16(1):28. doi: 10.1186/s12985-019-1135-7.

Abstract

BACKGROUND

HCV exhibits a high genetic diversity and is classified into 7 genotypes which are further divided into 86 confirmed subtypes. However, there are multiple isolates with unassigned subtypes. We aimed to amplify and characterize the full-length genome sequence of an HCV genotype 1 (HCV-1) divergent isolate (DE/17-0414) in Germany.

METHODS

The HCV infection was detected in an HIV-1-positive German female within an HCV/HIV-coinfection study using a commercially available antigen-antibody HCV ELISA kit and confirmed by an in-house quantitative real-time RT-PCR assay. Preliminary genotyping was done by sequencing and phylogenetic analysis on partial NS5B region. The full-length genome sequence was determined by consensus RT-PCR assays. Resistance-associated substitutions (RASs) were analyzed using the web-based tool Geno2pheno.

RESULTS

Partial NS5B region of the isolate DE/17-0414 showed more than 95% identity to 73-08460349-1 l and HCV_Fr_003 from France and QC316 from Canada. Full-length genome analysis of the DE/17-0414 strain showed 91.8% identity to QC316 but less than 79.6% to other HCV-1 strains. Phylogenetic analyses demonstrated that DE/17-0414, 73-08460349-1 l, HCV_Fr_003, and QC316 formed a separate subcluster within HCV-1. DE/17-0414 had a distinct 3 amino acids insertion at the N-terminal of hypervariable region 1 (HVR1) within viral envelope glycoprotein 2 (E2) and several potential antiviral RASs among the NS3 and NS5A genes.

CONCLUSIONS

We identified and analyzed an HCV-1 divergent isolate derived from an HIV-1 coinfected individual in Germany, which will be assigned to a new HCV-subtype 1o. Our understanding of the origin and transmission dynamics of this new subtype 1o requires further assessments from patients worldwide.

摘要

背景

HCV 具有高度的遗传多样性,分为 7 种基因型,进一步分为 86 种已确认的亚型。然而,还有多种未分配亚型的分离株。我们的目的是扩增和分析德国分离的 HCV 基因型 1(HCV-1)的全长基因组序列(HCV-1 分离株 DE/17-0414)。

方法

在 HCV/HIV 合并感染研究中,使用市售抗原抗体 HCV ELISA 试剂盒检测到一名 HIV-1 阳性的德国女性感染 HCV,并用内部定量实时 RT-PCR 检测证实。通过测序和系统发育分析对部分 NS5B 区进行初步基因分型。使用共识 RT-PCR 检测确定全长基因组序列。使用基于网络的工具 Geno2pheno 分析耐药相关取代(RAS)。

结果

分离株 DE/17-0414 的部分 NS5B 区与法国的 73-08460349-1 和 HCV_Fr_003 以及加拿大的 QC316 超过 95%同源。DE/17-0414 株全长基因组分析显示与 QC316 同源性为 91.8%,但与其他 HCV-1 株的同源性低于 79.6%。系统发育分析表明,DE/17-0414、73-08460349-1、HCV_Fr_003 和 QC316 在 HCV-1 内形成一个单独的亚群。DE/17-0414 在病毒包膜糖蛋白 2(E2)的高变区 1(HVR1)的 N 端有一个独特的 3 个氨基酸插入,在 NS3 和 NS5A 基因中有几个潜在的抗病毒 RAS。

结论

我们鉴定并分析了德国一名 HIV-1 合并感染个体的 HCV-1 分离株,该分离株将被分配到新的 HCV-1o 亚型。我们需要对来自世界各地的患者进行进一步评估,以了解这种新的 1o 亚型的起源和传播动态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ea/6399946/ac74db13b029/12985_2019_1135_Fig1_HTML.jpg

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