CD8+ T-cell exhaustion phenotype in chronic hepatitis C virus infection is associated with epitope sequence variation

During chronic hepatitis C virus (HCV) infection CD8+ T-cells become functionally exhausted, undergoing progressive phenotypic changes, i.e., overexpression of inhibitory molecules such as PD-1 (programmed cell death protein 1) and/or Tim-3 (T-cell immunoglobulin and mucin domain-containing molecule-3). The extreme intrahost genetic diversity of HCV is a major mechanism of immune system evasion, facilitating epitope escape. The aim of the study was to determine whether T-cell exhaustion phenotype in chronic HCV infection is related to the sequence repertoire of NS3 viral immunodominant epitopes.The dataset comprises original NGS fastq reads from 90 prospective patients with chronic HCV genotype 1b infection. Amplicons of 2223 bp, encompassing the NS3/4a viral genes of hepatitis C virus, (nt 3466-5689 according to H77 reference genome, GenBank: AF009606), covering epitopes NS31073, NS31406 and NS31436 encoding regions were tagmented using Nextera XT Sample preparation Kit (Illumina). Sequencing was performed on MiSeq (Illumina) platform using MiSeq Reagent v3 kit 2x300 bp, (Illumina).

在慢性丙型肝炎病毒（hepatitis C virus, HCV）感染进程中，CD8+ T细胞会发生功能耗竭，并伴随进行性表型改变，例如过度表达程序性细胞死亡蛋白1（programmed cell death protein 1）、T细胞免疫球蛋白黏蛋白域分子3（T-cell immunoglobulin and mucin domain-containing molecule-3）等抑制性分子。HCV宿主内极高的遗传多样性是其逃避免疫系统的主要机制，可促进表位逃逸。
本研究旨在明确慢性HCV感染中的T细胞耗竭表型是否与NS3病毒免疫显性表位的序列库相关。
本数据集包含90例慢性HCV 1b型感染前瞻性患者的原始下一代测序（next-generation sequencing, NGS）fastq读数。针对长度为2223 bp的扩增子——该扩增子涵盖HCV NS3/4a病毒基因（参照H77参考基因组GenBank: AF009606，对应核苷酸位置3466-5689），并覆盖NS3₁₀₇₃、NS3₁₄₀₆及NS3₁₄₃₆的编码区——使用Nextera XT样本制备试剂盒（Illumina公司）进行标签化建库。测序采用Illumina公司MiSeq平台，搭配MiSeq Reagent v3试剂盒，以2×300 bp双端测序模式完成。