Important roles of HBe and HBs antigens in the evasion of endogenous innate immune responses in Hepatitis B Virus infection.

HBe 和 HBs 抗原在乙型肝炎病毒感染中逃避内源性先天免疫反应中的重要作用。

• 批准号: 450164446
• 负责人: Privatdozentin Dr. Ruth Bröring
• 金额: --
• 依托单位: The State Key Laboratory of Virology
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/450164446?language=en
• 关键词: Important; roles; HBe; HBs; antigens

Host innate immunity is the body's first line of defense against viral infections. Clinical investigations have found that the level of interferon response in patients with hepatitis B virus (HBV) infection is low or almost undetectable. One of the causes is due to the strong ability of HBV proteins to inhibit the expression of endogenous interferons. HBV excretory (HBeAg) and HBV surface antigens (HBsAg) are two secretory proteins produced by HBV-infected cells. However, parts of HBeAg and HBsAg remain in infected host cells. This project will explore the molecular mechanism by which intracellular HBeAg and HBsAg affect the host cellular innate immune system including endogenous interferon responses using cell culture models, animal experiments and clinical specimens’ analysis and other strategies including HBV infection in primary human hepatocytes. We will investigate the interaction of viral proteins with the host adapter proteins of innate immune signaling and interferon pathways and the related downstream signaling, and study the regulatory effect of HBeAg and HBsAg on the expression of antiviral and inflammatory cytokines during HBV infection at the molecular level. Unveiling the mechanism behind the action of HBeAg and HBsAg in antagonizing endogenous antiviral responses during HBV infection, our research may provide a new idea for the future clinical treatment of hepatitis B virus infection.

宿主的先天免疫是人体抵御病毒感染的第一道防线。临床研究发现，乙肝病毒感染患者的干扰素应答水平很低，甚至几乎检测不到。其中一个原因是由于乙肝病毒蛋白具有很强的抑制内源性干扰素表达的能力。乙肝病毒排泄物(HBeAg)和表面抗原(HBs)是由乙肝病毒感染细胞产生的两种分泌性蛋白。然而，部分HBeAg和HBs Ag仍留在受感染的宿主细胞中。本项目将利用细胞培养模型、动物实验和临床标本分析以及其他策略，包括原代人类肝细胞中的乙肝病毒感染，探讨细胞内HBeAg和HBs Ag影响宿主细胞天然免疫系统的分子机制，包括内源性干扰素反应。我们将研究病毒蛋白与先天免疫信号和干扰素途径的宿主适配蛋白及相关下游信号的相互作用，并从分子水平研究HBeAg和HBs Ag对乙肝病毒感染过程中抗病毒和炎症细胞因子表达的调节作用。我们的研究揭示了HBeAg和HBs Ag在乙肝病毒感染过程中对抗内源性抗病毒反应的作用机制，为今后临床治疗乙肝病毒感染提供了新的思路。