IFNα subtype-specific susceptibility of HBV in the course of infection

慢性乙型肝炎病毒（HBV）感染仍然是世界范围内的一个主要健康问题，并且仍然难以治愈。干扰素α (IFNα)免疫治疗是慢性乙型肝炎临床治疗的重要方法。IFNα具有直接抗病毒作用和免疫调节活性，可在部分治疗的慢性乙型肝炎患者中诱导持续的抗病毒反应。然而，我们之前的研究表明，临床上使用的亚型（IFNα2）并不是所有IFNα亚型中抗hbv治疗最有效的亚型。迄今为止，对HBV感染过程中IFNα亚型特异性易感性及其相关的细胞和分子机制知之甚少。在目前的项目中，我们希望通过使用人体临床样本、体外细胞模型以及体内动物模型，首先研究在hbv感染患者的不同组织中诱导IFNA亚型，并将其与不同患者队列中的ISG表达模式相关联。我们还旨在研究特定的人类IFNα亚型对HBV cccDNA的抗病毒作用，这是根除HBV的主要障碍。在ifn介导的免疫疗法背景下，对HBV的免疫应答和个体细胞亚群的作用的进一步分析将被研究。研究结果将为设计新的靶向免疫治疗慢性乙型肝炎的策略提供理论和实验依据。

Chronic hepatitis B virus (HBV) infection continues to be a major health problem worldwide, and remains hard to be cured. Immunotherapy with Interferon α (IFNα) is an important method for the clinical treatment of chronic hepatitis B. IFNα exhibits direct antiviral effect as well as immunomodulatory activities, which can induce sustained antiviral responses in part of the treated chronic hepatitis B patients. However, our previous studies have demonstrated that the clinically used subtype (IFNα2) is not the most effective subtype for the anti-HBV treatment among all IFNα subtypes. So far very little is known about the IFNα subtype-specific susceptibility during the course of HBV infection and its related cellular and molecular mechanism. In the current project, by employing human clinical samples, in vitro cellular models as well as in vivo animal models, we want to firstly study the induction of IFNA subtypes in different tissues from HBV-infected patients and we will correlate this with ISG expression pattern in different patient cohorts. We also aim to investigate the antiviral effects of specific human IFNα subtypes on HBV cccDNA, which is a major hurdle in eradicating HBV. Further analysis of the immune response against HBV in the context of IFN-mediated immunotherapies and the role of individual cell subsets will be investigated. The results of the study will provide theoretical and experimental evidences for designing new targeted immunotherapeutic strategies for chronic hepatitis B infection.