乙型肝炎病毒与肝细胞的相互作用和天然免疫反应：实验模

StephenW

Hepatitis B Virus-Hepatocyte Interactions and Innate Immune Responses: Experimental Models and Molecular Mechanisms
Emmanuel Thomas  1   2   3 , Thomas F Baumert  4   5   6
Affiliations
Affiliations

    1
    Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida.
    2
    Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida.
    3
    Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.
    4
    Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.
    5
    Laboratory of Excellence HEPSYS, University of Strasbourg, Strasbourg, France.
    6
    Institut Hospitalo-Universitaire, Pôle hépato-digestif, Nouvel Hôpital Civil, Strasbourg, France.

    PMID: 31266064 PMCID: PMC7377277 DOI: 10.1055/s-0039-1685518

Free PMC article
Abstract

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide. While current therapeutic approaches can efficiently control viral infection, efficient curative antivirals are absent. The understanding of virus-hepatocyte interactions and sensing of viral infection is an important prerequisite for the development of novel antiviral therapies for cure. Hepatocyte intrinsic innate immunity provides a rapid first line of defense to combat viral infection through the upregulation of antiviral and inflammatory genes. However, the functional relevance of many of these antiviral signaling pathways in the liver and their role in HBV pathogenesis is still only partially understood. The recent identification of intracellular RNA and DNA sensing pathways and their involvement in disease biology, including viral pathogenesis and carcinogenesis, is currently transforming our understanding of virus-host interactions. Here the authors review the current knowledge on intrinsic antiviral innate immune responses including the role of viral nucleic acid sensing pathways in the liver. Since HBV has been designated as a "stealth virus," the study of the impact of HBV on signaling pathways in the hepatocyte is of significant interest to understand viral pathogenesis. Characterizing the mechanism underlying these HBV-host interactions and targeting related pathways to enhance antiviral innate responses may open new strategies to trigger noncytopathic clearance of covalently closed circular DNA to ultimately cure patients with chronic HBV infection.

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

StephenW

乙型肝炎病毒与肝细胞的相互作用和天然免疫反应：实验模型和分子机制。
伊曼纽尔·托马斯1 2 3，托马斯·鲍默特4 5 6
隶属关系
隶属关系

    1个
    迈阿密大学米勒医学院希夫肝病中心，佛罗里达州迈阿密。
    2
    佛罗里达州迈阿密市迈阿密大学米勒医学院的微生物学和免疫学系。
    3
    西尔维斯特综合癌症中心，迈阿密大学米勒医学院，佛罗里达州迈阿密。
    4
    法国，斯特拉斯堡，马拉维斯病毒和肝病研究中心，Inserm，U1110。
    5
    法国斯特拉斯堡斯特拉斯堡大学卓越HEPSYS实验室。
    6
    法国史特拉斯堡的NouvelHôpitalCivil医院大学医院研究所。

    PMID：31266064 PMCID：PMC7377277 DOI：10.1055 / s-0039-1685518

免费PMC文章
抽象

慢性乙型肝炎病毒（HBV）感染是全球范围内肝脏疾病和癌症的主要原因。尽管当前的治疗方法可以有效地控制病毒感染，但缺乏有效的抗病毒药物。对病毒-肝细胞相互作用的了解和对病毒感染的感知是开发新的抗病毒治疗药物的重要前提。肝细胞固有的先天免疫力通过抗病毒和炎性基因的上调，为抵抗病毒感染提供了快速的第一道防线。然而，肝脏中许多这些抗病毒信号通路的功能相关性及其在HBV发病机理中的作用仍仅被部分理解。最近对细胞内RNA和DNA传感途径的识别及其在疾病生物学中的参与，包括病毒的发病机理和致癌作用，目前正在改变我们对病毒-宿主相互作用的理解。在这里，作者回顾了有关内在抗病毒先天免疫应答的当前知识，包括病毒核酸传感途径在肝脏中的作用。由于乙肝病毒已被指定为“隐形病毒”，因此了解乙肝病毒对肝细胞信号通路的影响对于了解病毒的发病机理具有重大意义。表征这些HBV-宿主相互作用的基础机制并靶向相关途径以增强抗病毒先天反应可能会开启新的策略，以触发共价闭合环状DNA的无细胞清除，从而最终治愈慢性HBV感染患者。

美国纽约第七大道333号Thieme Medical Publishers，美国纽约。

StephenW

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