CK1α upregulates the IFNAR1 expression to prompt the anti-HBV effect of type I IFN in hepatoma carcinoma cells

Jing Xiong; Yanjun Jiang; Jinru Zhang; Yanmeng Chen; Yuan Hu

doi:10.1016/j.virs.2022.08.004

December 2022

. doi: 10.1016/j.virs.2022.08.004

Citation: Jing Xiong, Yanjun Jiang, Jinru Zhang, Yanmeng Chen, Yuan Hu. CK1α upregulates the IFNAR1 expression to prompt the anti-HBV effect of type I IFN in hepatoma carcinoma cells .VIROLOGICA SINICA, 2022, 37(6) : 894-903. http://dx.doi.org/10.1016/j.virs.2022.08.004

肝癌细胞中CK1α上调IFNAR1的表达，促进I型IFN抑制HBV复制

重庆医科大学感染性疾病分子生物学教育部重点实验室

通讯作者： 胡源, huyuan@cqmu.edu.cn
收稿日期： 2022-01-27
录用日期： 2022-08-08

摘要

酪蛋白激酶1α（CK1α）通过介导I型干扰素受体1（IFNAR1）的磷酸化和降解来应对病毒的感染。但是，CK1α如何调控乙肝病毒（HBV）复制以及IFN-α抗HBV作用的报道较少。本研究表明，在肝癌细胞中，CK1α可以与IFNAR1相互作用。在外源IFN-α抑制HBV过程中，CK1α通过降低IFNAR1的泛素化来增加IFNAR1的丰度水平，进一步促进IFN-α诱导的JAK-STAT信号通路，从而增强IFN-α抑制HBV复制的效应。我们的结果表明宿主因子CK1α促进了IFN-α抑制HBV复制的效应，为提高IFN-α治疗CHB的有效性提供新的思路。
- 乙型肝炎病毒
- , 酪蛋白激酶1α
- , I型干扰素受体1
- , 干扰素α

CK1α upregulates the IFNAR1 expression to prompt the anti-HBV effect of type I IFN in hepatoma carcinoma cells

Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China

Corresponding author: Yuan Hu, huyuan@cqmu.edu.cn
Received Date: 27 January 2022
Accepted Date: 08 August 2022

Abstract

Casein kinase 1α (CK1α) mediates the phosphorylation and degradation of interferon-α/β receptor 1 (IFNAR1) in response to viral infection. However, how CK1α regulates hepatitis B virus (HBV) replication and the anti-HBV effects of IFN-α are less reported. Here we show that CK1α can interact with IFNAR1 in hepatoma carcinoma cells and increased the abundance of IFNAR1 by reducing the ubiquitination levels in the presence of HBV. Furthermore, CK1α promotes the IFN-α triggered JAK-STAT signaling pathway and consequently enhances the antiviral effects of IFN-α against HBV replication. Our results collectively provide evidence that CK1α positively regulates the anti-HBV activity of IFN-α in hepatoma carcinoma cells, which would be a promising therapeutic target to improve the effectiveness of IFN-α therapy to cure CHB.
- Hepatitis B virus (HBV)
- , Casein kinase 1α (CK1α)
- , Interferon-α/β receptor 1 (IFNAR1)
- , Interferon-α (IFN-α)

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Electronic Supplementary Material

10.1016j.virs.2022.08.004-ESM.zip