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Hepatitis B Surface Antigen Suppresses the Activation of Nuclear Factor Kappa B Pathway via Interaction With the TAK1-TAB2 Complex

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 esca...

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Autores principales: Deng, Feiyan, Xu, Gang, Cheng, Zhikui, Huang, Yu, Ma, Caijiao, Luo, Chuanjin, Yu, Chen, Wang, Jun, Xu, Xiupeng, Liu, Shi, Zhu, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947203/
https://www.ncbi.nlm.nih.gov/pubmed/33717111
http://dx.doi.org/10.3389/fimmu.2021.618196
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author Deng, Feiyan
Xu, Gang
Cheng, Zhikui
Huang, Yu
Ma, Caijiao
Luo, Chuanjin
Yu, Chen
Wang, Jun
Xu, Xiupeng
Liu, Shi
Zhu, Ying
author_facet Deng, Feiyan
Xu, Gang
Cheng, Zhikui
Huang, Yu
Ma, Caijiao
Luo, Chuanjin
Yu, Chen
Wang, Jun
Xu, Xiupeng
Liu, Shi
Zhu, Ying
author_sort Deng, Feiyan
collection PubMed
description 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.
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spelling pubmed-79472032021-03-12 Hepatitis B Surface Antigen Suppresses the Activation of Nuclear Factor Kappa B Pathway via Interaction With the TAK1-TAB2 Complex Deng, Feiyan Xu, Gang Cheng, Zhikui Huang, Yu Ma, Caijiao Luo, Chuanjin Yu, Chen Wang, Jun Xu, Xiupeng Liu, Shi Zhu, Ying Front Immunol Immunology 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. Frontiers Media S.A. 2021-02-25 /pmc/articles/PMC7947203/ /pubmed/33717111 http://dx.doi.org/10.3389/fimmu.2021.618196 Text en Copyright © 2021 Deng, Xu, Cheng, Huang, Ma, Luo, Yu, Wang, Xu, Liu and Zhu http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Deng, Feiyan
Xu, Gang
Cheng, Zhikui
Huang, Yu
Ma, Caijiao
Luo, Chuanjin
Yu, Chen
Wang, Jun
Xu, Xiupeng
Liu, Shi
Zhu, Ying
Hepatitis B Surface Antigen Suppresses the Activation of Nuclear Factor Kappa B Pathway via Interaction With the TAK1-TAB2 Complex
title Hepatitis B Surface Antigen Suppresses the Activation of Nuclear Factor Kappa B Pathway via Interaction With the TAK1-TAB2 Complex
title_full Hepatitis B Surface Antigen Suppresses the Activation of Nuclear Factor Kappa B Pathway via Interaction With the TAK1-TAB2 Complex
title_fullStr Hepatitis B Surface Antigen Suppresses the Activation of Nuclear Factor Kappa B Pathway via Interaction With the TAK1-TAB2 Complex
title_full_unstemmed Hepatitis B Surface Antigen Suppresses the Activation of Nuclear Factor Kappa B Pathway via Interaction With the TAK1-TAB2 Complex
title_short Hepatitis B Surface Antigen Suppresses the Activation of Nuclear Factor Kappa B Pathway via Interaction With the TAK1-TAB2 Complex
title_sort hepatitis b surface antigen suppresses the activation of nuclear factor kappa b pathway via interaction with the tak1-tab2 complex
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947203/
https://www.ncbi.nlm.nih.gov/pubmed/33717111
http://dx.doi.org/10.3389/fimmu.2021.618196
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