Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
Department of Applied Chemistry, Kyung Hee University, Yongin, Gyeonggi, Korea.
Gut. 2018 Jan;67(1):166-178. doi: 10.1136/gutjnl-2016-312742. Epub 2017 Mar 23.
Interferons (IFNs) mediate direct antiviral activity. They play a crucial role in the early host immune response against viral infections. However, IFN therapy for HBV infection is less effective than for other viral infections.
We explored the cellular targets of HBV in response to IFNs using proteome-wide screening.
Using LC-MS/MS, we identified proteins downregulated and upregulated by IFN treatment in HBV X protein (HBx)-stable and control cells. We found several IFN-stimulated genes downregulated by HBx, including , which is known as an antiretroviral protein. We demonstrated that HBx suppresses the transcription of through a single CpG methylation in its 5'-UTR, which further reduces the IFN regulatory factor-1 binding affinity, thereby suppressing the IFN-stimulated induction of .
We verified our findings using a mouse model, primary human hepatocytes and human liver tissues. Our data elucidate a mechanism by which HBV evades the host innate immune system.
干扰素 (IFN) 具有直接抗病毒活性。它们在宿主对病毒感染的早期免疫反应中起着至关重要的作用。然而，IFN 治疗乙型肝炎病毒 (HBV) 感染的效果不如其他病毒感染。
我们使用蛋白质组范围筛选来研究 IFN 作用下 HBV 的细胞靶标。
通过 LC-MS/MS，我们鉴定了 HBV X 蛋白 (HBx) 稳定和对照细胞中 IFN 处理下调和上调的蛋白。我们发现了几个被 HBx 下调的 IFN 刺激基因，包括 ，它是一种抗病毒蛋白。我们证明 HBx 通过其 5'UTR 中的单个 CpG 甲基化抑制 的转录，这进一步降低了 IFN 调节因子-1 的结合亲和力，从而抑制了 IFN 刺激的诱导。
我们使用小鼠模型、原代人肝细胞和人肝组织验证了我们的发现。我们的数据阐明了 HBV 逃避宿主先天免疫系统的机制。
