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

宿主的先天免疫是机体抵御病毒感染的第一道防线。临床研究发现，B型肝炎病毒（HBV）感染患者的干扰素应答水平较低或几乎检测不到。原因之一是由于HBV蛋白质抑制内源性干扰素表达的强大能力。乙型肝炎病毒排泄抗原（HBeAg）和乙型肝炎病毒表面抗原（HBsAg）是由乙型肝炎病毒感染的细胞产生的两种分泌蛋白。然而，部分HBeAg和HBsAg仍留在感染的宿主细胞中。本项目将利用细胞培养模型、动物实验和临床标本分析等手段，包括HBV感染原代人肝细胞等，探讨细胞内HBeAg和HBsAg影响宿主细胞天然免疫系统的分子机制，包括内源性干扰素应答。我们将研究病毒蛋白与宿主天然免疫信号通路和干扰素通路衔接蛋白的相互作用及其下游信号通路，并从分子水平研究HBeAg和HBsAg对HBV感染过程中抗病毒和炎症细胞因子表达的调节作用。本研究揭示了HBeAg和HBsAg拮抗HBV感染时内源性抗病毒反应的机制，为今后临床治疗B病毒感染提供了新的思路。

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.