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

慢性乙肝病毒感染仍然是世界范围内的一个主要健康问题，而且仍然很难治愈。干扰素α免疫治疗是临床治疗慢性乙型病毒性肝炎的重要方法，干扰素α具有直接的抗病毒作用和免疫调节活性，可在部分慢性乙肝患者体内诱导持续的抗病毒反应。然而，我们以前的研究表明，在所有干扰素α亚型中，临床使用的干扰素α2亚型并不是最有效的抗乙肝治疗亚型。到目前为止，关于干扰素在α感染过程中的亚型特异性易感性及其相关的细胞和分子机制还知之甚少。在本项目中，我们希望通过使用人类临床样本、体外细胞模型以及体内动物模型，首先研究乙肝患者不同组织中IFNA亚型的诱导，并将其与ISG在不同患者队列中的表达模式相关联。我们还旨在研究特定的人干扰素α亚型对HBVcccDNA的抗病毒作用，这是根除HBVcccDNA的主要障碍。在干扰素介导的免疫疗法和单个细胞亚群的作用的背景下，将进一步分析针对乙肝病毒的免疫反应。本研究结果将为设计新的慢性乙型肝炎靶向免疫治疗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.