Liver Center at the Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Viruses. 2019 Jul 26;11(8):683. doi: 10.3390/v11080683.
The hepatitis C virus is unique among chronic viral infections in that an acute outcome with complete viral elimination is observed in a minority of infected patients. This unique feature allows direct comparison of successful immune responses with those that fail in the setting of the same human infection. Here we review how this scenario can be used to achieve better understanding of transcriptional regulation of T-cell differentiation. Specifically, we discuss results from a study comparing transcriptional profiles of hepatitis C virus (HCV)-specific CD8 T-cells during early HCV infection between patients that do and do not control and eliminate HCV. Identification of early gene expression differences in key T-cell differentiation molecules as well as clearly distinct transcriptional networks related to cell metabolism and nucleosomal regulation reveal novel insights into the development of exhausted and memory T-cells. With additional transcriptional studies of HCV-specific CD4 and CD8 T-cells in different stages of infection currently underway, we expect HCV infection to become a valuable model disease to study human immunity to viruses.
丙型肝炎病毒在慢性病毒感染中是独特的，因为少数感染患者会出现完全清除病毒的急性结果。这种独特的特征使得可以在相同的人体感染背景下直接比较成功的免疫反应和失败的免疫反应。在这里，我们回顾了如何利用这种情况来更好地理解 T 细胞分化的转录调控。具体来说，我们讨论了一项研究的结果，该研究比较了在 HCV 感染早期，具有不同 HCV 控制和清除能力的患者中 HCV 特异性 CD8 T 细胞的转录谱。在关键 T 细胞分化分子中的早期基因表达差异的鉴定，以及与细胞代谢和核小体调节相关的明确不同的转录网络，揭示了衰竭和记忆 T 细胞发育的新见解。随着目前正在进行的不同感染阶段的 HCV 特异性 CD4 和 CD8 T 细胞的更多转录研究，我们预计 HCV 感染将成为研究人类对病毒免疫的有价值的模型疾病。
