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

HBV感染过程中IFNα亚型特异性易感性

• 批准号: 410256219
• 负责人: Privatdozentin Dr. Kathrin Sutter
• 金额: --
• 依托单位: Department of Infectious Diseases
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/410256219?language=en
• 关键词: IFN; subtype; specific; susceptibility; HBV

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.

慢性B型肝炎病毒（HBV）感染仍然是世界范围内的主要健康问题，并且仍然难以治愈。α干扰素（IFNα）免疫治疗是临床治疗慢性B型肝炎的重要手段。IFNα具有直接的抗病毒作用和免疫调节作用，可诱导部分慢性B型肝炎患者产生持续的抗病毒应答。然而，我们以前的研究表明，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的了解甚少。在本项目中，通过使用人类临床样本、体外细胞模型以及体内动物模型，我们希望首先研究HBV感染患者的不同组织中IFNA亚型的诱导，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人IFNα亚型对HBV cccDNA的抗病毒作用，这是根除HBV的主要障碍。将进一步分析IFN介导的免疫治疗背景下对HBV的免疫应答以及单个细胞亚群的作用。本研究结果将为设计慢性B型肝炎的靶向免疫治疗新策略提供理论和实验依据。