乙型肝炎表面抗原通过与TAK1-TAB2复合体的相互作用抑制核因

StephenW

Hepatitis B Surface Antigen Suppresses the Activation of Nuclear Factor Kappa B Pathway via Interaction With the TAK1-TAB2 Complex
Feiyan Deng  1 , Gang Xu  1 , Zhikui Cheng  1 , Yu Huang  1 , Caijiao Ma  1 , Chuanjin Luo  1 , Chen Yu  1 , Jun Wang  2 , Xiupeng Xu  3 , Shi Liu  1 , Ying Zhu  1
Affiliations
Affiliations

    1
    State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
    2
    Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
    3
    Department of Clinical Laboratory, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic, Huangshi, China.

    PMID: 33717111 PMCID: PMC7947203 DOI: 10.3389/fimmu.2021.618196

Abstract

Chronic hepatitis B is a major health problem worldwide, with more than 250 million chronic carriers. Hepatitis B virus interferes with the host innate immune system so as to evade elimination via almost all of its constituent proteins; nevertheless, the function of HBsAg with respect to immune escape remains unclear. This study aimed to determine the role HBsAg plays in assisting HBV to escape from immune responses. We found that HBsAg suppressed the activation of the nuclear factor kappa B (NF-кB) pathway, leading to downregulation of innate immune responses. HBsAg interacted with TAK1 and TAB2 specifically, inhibiting the phosphorylation and polyubiquitination of TAK1 and the K63-linked polyubiquitination of TAB2. Autophagy is a major catabolic process participating in many cellular processes, including the life cycle of HBV. We found that HBsAg promoted the autophagic degradation of TAK1 and TAB2 via the formation of complexes with TAK1 and TAB2, resulting in suppression of the NF-κB pathway. The expression of TAK1, TAB2, and the translocation of NF-κB inversely correlated with HBsAg levels in clinical liver tissues. Taken together, our findings suggest a novel mechanism by which HBsAg interacts with TAK1-TAB2 complex and suppresses the activation of NF-κB signaling pathway via reduction of the post-translational modifications and autophagic degradation.

Keywords: TAK1-TAB2; autophagic degradation; hepatitis B surface antigen; immune escape; phosphorylation; polyubiquitination.

Copyright © 2021 Deng, Xu, Cheng, Huang, Ma, Luo, Yu, Wang, Xu, Liu and Zhu.

StephenW

乙型肝炎表面抗原通过与TAK1-TAB2复合体的相互作用抑制核因子Kappa B途径的激活。
邓飞燕1，徐刚1，智之城1，黄玉1，才叫马1，罗志金1，陈宇1，王军2，秀鹏旭3，石柳1，应营1
隶属关系
隶属关系

    1个
    武汉大学生命科学学院，病毒学国家重点实验室，现代病毒学研究中心，武汉，中国。
    2个
    华中科技大学同济医学院附属同济医院病理科，武汉。
    3
    湖北职业技术学院附属医院黄石市中心医院检验科。

    PMID：33717111 PMCID：PMC7947203 DOI：10.3389 / fimmu.2021.618196

抽象的

慢性乙型肝炎是全球主要的健康问题，拥有超过2.5亿慢性携带者。乙型肝炎病毒会干扰宿主的先天免疫系统，从而通过其几乎所有组成蛋白逃避清除。然而，HBsAg在免疫逃逸方面的功能仍不清楚。这项研究旨在确定HBsAg在协助HBV摆脱免疫反应中所起的作用。我们发现HBsAg抑制了核因子κB（NF-кB）通路的激活，导致先天免疫反应的下调。 HBsAg特异性地与TAK1和TAB2相互作用，从而抑制TAK1的磷酸化和多聚泛素化以及K63连接的TAB2的多聚泛素化。自噬是参与许多细胞过程（包括HBV生命周期）的主要分解代谢过程。我们发现HBsAg通过与TAK1和TAB2形成复合物而促进了TAK1和TAB2的自噬降解，从而抑制了NF-κB途径。 TAK1，TAB2的表达以及NF-κB的易位与临床肝组织中HBsAg水平呈负相关。综上所述，我们的发现提出了一种新的机制，HBsAg通过该机制与TAK1-TAB2复合物相互作用，并通过减少翻译后修饰和自噬降解来抑制NF-κB信号通路的激活。

关键字：TAK1-TAB2;自噬降解乙型肝炎表面抗原；免疫逃逸；磷酸化多泛素化。

版权所有©2021邓，徐，成，黄，马，罗，于，王，徐，刘和朱。

StephenW

https://www.frontiersin.org/arti ... mmu.2021.618196/pdf