自噬在泛素化乙型肝炎病毒核心抗原增强树突状细胞功能中

StephenW

自噬在泛素化乙型肝炎病毒核心抗原增强树突状细胞功能中的作用
黄润1、陈洁1、谭全辉1、胡薇薇1、陈晓华1、于永生1、藏国庆1、唐正浩1
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联系

    1
    【作者单位】： 上海交通大学医学院附属第六人民医院感染科;

    PMID: 36315216 DOI: 10.1089/vim.2022.0062

抽象的

树突状细胞（DCs）作为最强大的抗原呈递细胞，在适应性免疫反应中发挥着关键作用，而树突状细胞的功能缺陷是对乙型肝炎病毒（HBV）感染产生免疫耐受的重要因素。乙型肝炎病毒核心抗原 (HBcAg) 是一种高抗原性蛋白，可诱导针对 HBV 的强烈抗原特异性免疫反应。在本研究中，我们首先构建了泛素化 HBcAg 基因 (UbHBcAg)，然后利用重组慢病毒载体 UbHBcAg (LV-UbHBcAg) 探索它们在 DC 自噬和功能中的作用。同时，进一步分析了自噬对DC功能激活的影响。最后，我们研究了 LV-UbHBcAg 诱导的自噬的潜在机制。结果表明，LV-UbHBcAg 可促进 DCs 自噬进程，上调的自噬可进一步促进 DC 功能成熟。此外，p62 可能在自噬降解中起重要作用。更重要的是，PI3K/Akt/mTOR信号通路参与了LV-UbHBcAg诱导的自噬过程。这些发现表明，LV-UbHBcAg 可以通过诱导自噬来激活 DC 功能，这可能代表了一种治疗慢性 HBV 感染的有希望的策略。

关键词：PI3K/Akt/mTOR信号通路；自噬；树突状细胞；乙型肝炎病毒核心抗原；无处不在。

StephenW

Role of Autophagy in the Ubiquitinated Hepatitis B Virus Core Antigen Enhancing Dendritic Cell Function
Run Huang  1 , Jie Chen  1 , Quanhui Tan  1 , Weiwei Hu  1 , Xiaohua Chen  1 , Yongsheng Yu  1 , Guoqing Zang  1 , Zhenghao Tang  1
Affiliations
Affiliation

    1
    Department of Infectious Disease, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

    PMID: 36315216 DOI: 10.1089/vim.2022.0062

Abstract

Dendritic cells (DCs), as the most powerful antigen-presenting cells, play a key role in the adaptive immune response, while the defective function of DC is an important factor in immune tolerance to hepatitis B virus (HBV) infection. Hepatitis B virus core antigen (HBcAg) is a highly antigenic protein that can induce a strong antigen-specific immune response against HBV. In this study, we first constructed the ubiquitinated HBcAg gene (UbHBcAg), and then utilized a recombinant lentiviral vector UbHBcAg (LV-UbHBcAg) to explore the role of them in DC autophagy and function. Meanwhile, the effects of autophagy on DC functional activation were further analyzed. Finally, we investigated the underlying mechanism of autophagy induced by LV-UbHBcAg. Results showed that LV-UbHBcAg could promote autophagic progression in DCs, and the upregulated autophagy can further enhance DC functional maturation. In addition, p62 may serve as an important role in autophagy degradation. More importantly, the PI3K/Akt/mTOR signaling pathway was involved in the process of autophagy induced by LV-UbHBcAg. These findings suggest that LV-UbHBcAg can activate DC function by inducing autophagy, which may represent a promising strategy to treat chronic HBV infection.

Keywords: PI3K/Akt/mTOR signaling pathway; autophagy; dendritic cells; hepatitis B virus core antigen; ubiquitinated.