III型干扰素诱导的CBFβ通过劫持HBx来抑制HBV复制

StephenW

Cell Mol Immunol. 2018 Mar 9. doi: 10.1038/s41423-018-0006-2. [Epub ahead of print]
Type III interferon-induced CBFβ inhibits HBV replication by hijacking HBx.
Xu F1, Song H1, Xiao Q2, Li N3, Zhang H4, Cheng G1, 5,6, Tan G7.
Author information

1
    Department of Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130061, China.
2
    Department of Nephrology, The First Hospital, Jilin University, Changchun, Jilin, 130021, China.
3
    Department of Obstetrics, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
4
    Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, 130021, China.
5
    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
6
    Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, 215123, China.
7
    Department of Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130061, China. [email protected].

Abstract

Hepatitis B virus (HBV) and its associated seamless studies of worldwide wellbeing threat of worldwide. yet, there is no impactful approach for clinical treatment of hepatitis B patients. developing, better a better understanding of the interactions between HBV and its host HBV infection has been reported to induce type-III but not type-I or type-II interferon (IFN). In this study, we identified CBFβ, an HIV enhancer, as an HBV restriction factor that is specifically induced by type-III IFN in the early stages of HBV infection. Type-III IFN-induced IL-10 played an important role in the production of CBFβ. Interestingly, the interaction between CBFβ- and HBV-encoded regulatory protein X (HBx) enhanced the stability of CBFβ. , but notably blocked HBx-mediated promotion of HBV replication. CBFβ expression was lower in HBV patients than in healthy persons, and the addition of serum from HBV patients inhibited CBFβ expression in HepG2 cells. On the In contrast, HBV via HBsAg inhibited type-III IFN-induced CBFβ expression and decreased the anti-HBV activity of type-III IFN, suggesting that HBV inhibits antiviral interferon-stimulated gene (ISG) expression and induces IFN resistance. Collectively, our values ​​represents That type-III IFN-triggered and IL-10-induced CBFβ are are factors for inhibiting HBV replication, and the HBx-CBFβ-HBsAg axis reveals a new molecular mechanism of interaction between HBV and its hosts.
PMID:29523836DOI:10.1038/s41423-018-0006-2

StephenW

Cell Mol Immunol。 2018年3月9日，doi：10.1038 / s41423-018-0006-2。 [电子版提前打印]
III型干扰素诱导的CBFβ通过劫持HBx来抑制HBV复制。
徐F1，宋H1，肖Q2，李N3，张H4，程G1，5,6，谭G7。
作者信息

1
吉林大学第一医院转化医学研究所免疫学教研室，吉林长春130061
2
吉林大学第一医院肾内科，吉林长春130021
3
吉林大学第一医院产科，吉林长春，130021
4
吉林大学第一医院第一临床研究中心，吉林，吉林，130021
五
美国加利福尼亚大学洛杉矶分校微生物学，免疫学和分子遗传学系，美国加州，90095。
6
中国医学科学院和中国协和医科大学基础医学研究所系统医学中心，北京100005;苏州市系统医学研究所，江苏苏州215123。
7
吉林大学第一医院转化医学研究所免疫学教研室，吉林长春130061 [email protected]。

抽象

乙型肝炎病毒（HBV）及其相关的关于世界范围内全球健康威胁的无缝研究。然而，对于乙型肝炎患者的临床治疗没有影响。据报道，更好地了解HBV与其宿主HBV感染之间的相互作用，已经报道诱导了III型而不是I型或II型干扰素（IFN）。在本研究中，我们将HIV增强子CBFβ鉴定为在HBV感染早期由III型IFN特异性诱导的HBV限制因子。 III型IFN诱导的IL-10在CBFβ的产生中起重要作用。有趣的是，CBFβ和HBV编码的调节蛋白X（HBx）之间的相互作用增强了CBFβ的稳定性。 ，但显着阻断HBx介导的HBV复制促进作用。 HBV患者的CBFβ表达水平低于健康人，并且HBV患者血清的添加抑制HepG2细胞中CBFβ的表达。相反，乙肝病毒通过HBsAg抑制III型IFN诱导的CBFβ表达并降低III型IFN的抗HBV活性，表明HBV抑制抗病毒干扰素刺激基因（ISG）的表达并诱导IFN抗性。总的来说，我们的观点表明，III型IFN诱导的和IL-10诱导的CBFβ是抑制HBV复制的因子，而HBx-CBFβ-HBsAg轴揭示了HBV与其宿主之间相互作用的新分子机制。