丙型肝炎病毒感染并扰乱肝干细胞。

Hepatitis C virus infects and perturbs liver stem cells.

机构信息

Gladstone Institute of Virology, San Francisco, California, USA.

Department of Electrical Engineering and Computer Science and Center for Computational Biology, University of California Berkeley, Berkeley, California, USA.

出版信息

mBio. 2023 Dec 19;14(6):e0131823. doi: 10.1128/mbio.01318-23. Epub 2023 Nov 8.

DOI:10.1128/mbio.01318-23

PMID:37938000

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10746249/

Abstract

The hepatitis C virus (HCV) causes liver disease, affecting millions. Even though we have effective antivirals that cure HCV, they cannot stop terminal liver disease. We used an adult stem cell-derived liver organoid system to understand how HCV infection leads to the progression of terminal liver disease. Here, we show that HCV maintains low-grade infections in liver organoids for the first time. HCV infection in liver organoids leads to transcriptional reprogramming causing cancer cell development and altered immune response. Our finding shows how HCV infection in liver organoids mimics HCV infection and patient pathogenesis. These results reveal that HCV infection in liver organoids contributes to liver disease progression.

摘要

丙型肝炎病毒 (HCV) 可导致肝脏疾病，影响数百万人。尽管我们有有效的抗病毒药物可以治愈 HCV，但它们无法阻止终末期肝病。我们使用成人干细胞衍生的肝类器官系统来了解 HCV 感染如何导致终末期肝病的进展。在这里，我们首次表明 HCV 在肝类器官中维持低度感染。肝类器官中的 HCV 感染导致转录重编程，导致癌细胞发育和免疫反应改变。我们的发现表明 HCV 感染肝类器官如何模拟 HCV 感染和患者发病机制。这些结果表明 HCV 感染肝类器官导致肝病进展。