土拨鼠肝炎病毒感染模型在乙型肝炎研究中的应用  

Applications of the woodchuck model of hepatitis virus infection in studies on hepatitis B

作　　者：艾灵 朱彬 王俊忠 陆蒙吉 杨东亮[1] 王宝菊[1] AI Ling;ZHU Bin;WANG Junzhong;LU Mengji;YANG Dongliang;WANG Baoju(Department of Infectious Diseases,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Institute of Virology,University of Duisburg-Essen, Essen D-45122,Germany)

机构地区：[1]华中科技大学同济医学院附属协和医院感染性疾病科,武汉430022 [2]德国Duisburg-Essen大学医院病毒研究所,德国埃森d45122

出　　处：《中国实验动物学报》2018年第5期649-655,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家传染病科技重大专项(2008ZX10002011;2012ZX10004503;2017ZX10304402-002-005);国家自然科学基金(81101248;81371828;81461130019);国家国际科技合作计划(2011DFA31030);国家科技支撑计划课题(2015BAI09B06)~~

摘　　要：乙型肝炎病毒(hepatitis B virus, HBV)是嗜肝DNA病毒的原型,HBV感染所致的乙型肝炎是严重危害我国人民身体健康的公共卫生问题。现有的抗乙肝药物包括核苷类似物和干扰素均难以达到临床治愈,研究新的抗乙肝药物、评价新的联合治疗策略均离不开合适的动物模型。土拨鼠肝炎病毒(woodchuck hepatitis virus, WHV)于1978年美国费城动物园患肝癌的土拨鼠中首次被发现,因其基因组结构、复制周期与HBV高度近似,被归类为嗜肝DNA病毒。WHV感染土拨鼠后的自然史与HBV感染人高度近似,因此土拨鼠模型很早就被用于乙肝DNA疫苗、抗HBV药物的评价。近年来土拨鼠多种细胞因子及其受体、免疫细胞表面标志先后被克隆和鉴定,T细胞应答的检测方法包括淋巴细胞增殖实验、CD107a脱颗粒实验逐步被建立,大大促进了土拨鼠模型在HBV发病机制及免疫调节治疗中的应用。本文主要综述了WHV感染土拨鼠模型的免疫学特征,以及该模型在抗乙肝病毒药物评价和免疫调节治疗中的应用。Hepatitis B virus(HBV)is a prototype of hepadnavirus,and hepatitis B caused by HBV infection is a serious public health problem.Using the currently available anti-HBV drugs,including nucleotide analogs and interferon-α,it is difficult to achieve a“clinical cure”endpoint.Thus,new anti-HBV drugs and combination therapy strategies are urgently needed,as are appropriate animal models for preclinical evaluations.Woodchuck hepatitis virus(WHV)was first discovered in woodchucks at the Philadelphia Zoo in the United States in 1978,and has been classified as hepadnavirus due to its comparable genomic structure and replication cycle with HBV.Furthermore,the natural history of WHV infection in woodchucks is highly similar to that of HBV infection in humans;therefore the woodchuck model has been used to evaluate HBV DNA vaccines and anti-HBV drugs for decades.In recent years,many cytokines,their receptors,and other immune cell surface markers have been cloned and identified.Additionally,detection method for T cell responses,including lymphocyte proliferation assays and CD107a degranulation assays,have been established and have greatly promoted the woodchuck model for studies of the immune-pathogenesis and immunomodulatory therapy of HBV infection.This review summarizes the immunological features of the WHV-infected woodchuck model and its application for evaluating anti-HBV drugs and immunomodulation therapies.

关 键 词：土拨鼠 旱獭 土拨鼠肝炎病毒 乙型肝炎病毒 动物模型 

分 类 号：Q95-33[生物学—动物学]