丙型肝炎病毒细胞模型和动物模型的研究

建立丙型肝炎病毒(HCV)的细胞模型及动物模型,对于深入认识HCV病原学特点、复制及发病机制,筛选有效药物及疫苗等极为重要。近年来,国内外学者作了大量探讨,概括如下。 1 HCV细胞模型的研究 1.1 HCV感染类细胞模型 1.1.1 以肝细胞为宿主的HCV感染细胞模型 众所周知,人肝细胞是HCV感染的天然宿主细胞,以成人肝细胞作为感染HCV的细胞模型应有更好的代表性。Ito等直接将HCV阳性血清与丙肝患者肝活检分离出来的肝细胞共培养,发现肝细胞内和培养上清液中可检出大量HCV RNA,用     

丙型肝炎病毒核心蛋白作用研究进展

丙型肝炎病毒(hepatitis C virus,HCV)是一种主要经过血液传播的肝炎病毒,是造成慢性肝炎、肝硬化甚至肝癌的主要原因之一.目前人们对HCV的致病机制的认识仍不很清楚,也缺乏针对HCV有效的治疗方法及疫苗预防.近年研究发现HCV核心(Core,C)蛋白除作为核壳体蛋白具有病毒颗粒组装功能外,还参与调节细胞凋亡、脂代谢、转录以及抗原呈递等作用,与干扰素抵抗也有密切关系.HCV C蛋白具有广泛的反式激活作用,与宿主细胞蛋白相互作用,是导致病毒持续性感染以及肝细胞癌发生的重要原因.深入认知和分析HCV C蛋白分子生物学特性,对阐明HCV持续性感染与致癌机制以及HCV对肝细胞脂肪变与干扰素疗效的影响等诸多问题具有重要意义.     

丙型肝炎病毒蛋白在转基因模型中的作用机制研究进展

丙型肝炎病毒(hepatitis C virus,HCV)与肝炎、肝硬化和肝癌的发生密切相关.由于HCV通常只在人和高级灵长类动物中形成自然感染,因此极少有研究建立HCV长期感染的实验室模型,HCV感染的病理生理学变化及其与宿主相互作用的相关研究也因此受到限制.近年来,转基因技术为研究人类疾病的分子机制提供了方法,在此基础上开展的转基因细胞系,嵌合体和转基因动物模型在感染性疾病研究中的价值已得到证实.本文综述了近年来HCV转基因模型中HCV蛋白相关的可能致病机制.     

丙型肝炎病毒编码蛋白的生物学功能

丙型肝炎是由丙型肝炎病毒(hepatitis C virus,HCV)引起的传染性疾病.是慢性肝病的主要原因之一,本文系统阐述病毒编码蛋白通过直接与细胞内重要调节分子结合,以病毒-宿主细胞相互作用方式影响细胞重要的信号通路,导致细胞增殖、分化等发生异常,干扰机体免疫防御功能,削弱宿主对HCV感染细胞的抗病毒应答,有利于慢性持续性感染的建立,最终促使HCV相关肝病的发生和发展.加强对病毒蛋白生物学功能的研究,将有助于探讨HCV致病机制和免疫逃逸机制,对HCV特异靶向药物和治疗性疫苗的研究和开发也具有重要的意义.     

戊型肝炎

东莞市石龙镇宾馆职工戊型肝炎病毒感染的流行病学调查报告，稳定表达HCV 1a NS5A和NSSA-△ISDR细胞株的构建，丙型肝炎病毒ns3区全长基因在大肠杆菌中的高效表达及纯化，部分藏、回、汉族献血员HCV感染的T细胞亚群变化在肝损伤中的作用，树突状细胞与丙型肝炎病毒感染研究，丙型肝炎病毒逃避宿主免疫的机制(综述)。     

宿主遗传基因多态性与丙型肝炎病毒感染转归的关系

丙型肝炎病毒(hepatitis C virus,HCV)急性感染后可引起机体一系列固有及适应性免疫反应.约有15%-25%的HCV感染可被宿主免疫反应所自限清除,而大多数则呈慢性持续性感染,发展为慢性活动性肝炎、肝硬化及肝细胞癌.大量研究证实宿主遗传基因的多态性可能会导致机体免疫功能状态的差异,进而影响到HCV感染的不同临床结局.本文主要对相关的潜在基因多态性与HCV感染转归的关系进行综述.     

丙型肝炎病毒受体研究的现状及展望

在HCV感染宿主过程中,病毒必须首先结合到靶细胞表面,经受体的介导进入细胞,然后才能复制,引起相关的病理变化;因此如何终止丙型肝炎的慢性化进展,特别是阻断HCV的感染过程是关键的问题[1]。阻断HCV感染首先涉及到宿主细胞表面的HCV受体或辅助受体,相关的研究刚开始。现在初步研究结果证实:丙型肝炎病毒的包膜蛋白E1和E2可能是和靶细胞结合的配体,导致病毒进入宿主细胞。由于HCV基因的变异主要反映在病毒包膜E2蛋白,所以E2蛋白的高变区（HVR）决定了     

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自丙型肝炎病毒(hepatitis C virus,HCV)发现以来,关于其病毒学的研究不断取得一些进展,这些进展主要依赖于对其分子生物学的研究以及对其相关基因表达产物的研究。而关于HCV的形态还没有取得一致的可重复性的结论。这些HCV病毒学的进展主要在以下几方面与临床有关。1抗HCV药物筛选模型的建立病毒的复制有赖于感染活的宿主细胞,为了建立有效的抗HCV复制药物的细胞筛选模型,迫切需要建立能够允许HCV持续感染并有效复制的细胞系,但HCV RNA感染或转染原代培养的肝细胞、传代非瘤肝细胞系(PH5CH)、肝癌细胞系(Huh7)、逆转录病毒感染…     

丙型肝炎病毒核心蛋白——免疫逃逸的“核心”？

丙型肝炎病毒（HCV）的特性是可以引起大多数病人的慢性感染。这主要是由于宿主免疫系统无法清除最初的HCV感染。强大的HCV特异性CD4＋和CDg＋T细胞活化与急性感染的清除有关，同时在慢性感染中，针对许多病毒决定基的HCV特异性T细胞的克隆是存在的，但其发生率低且没有发挥有效的功能。慢性HCV感染的异常免疫应答包括固有免疫系统的不完全活化，如单核细胞产生过度的炎性级联反应以及树突状细胞（DC）功能的改变。     

丙型肝炎病毒非结构蛋白NS3致肝癌机制的研究进展

大量研究显示丙型肝炎病毒(hepatitis C virus,HCV)持续感染肝细胞能导致肝细胞癌(hepatocellular carcinoma,HCC),但其致癌机制目前还不十分清楚.HCV是一种RNA病毒,其基因组不能整合到宿主染色体中引起基因突变,可能是通过其表达的蛋白质引起细胞转化.由于HCV NS3含有多种蛋白酶活性,因而推测HCV NS3在肝细胞癌的形成过程中具有重要作用,本文就HCV NS3致癌机制的研究进展作一综述.     

Effects of HCV proteins in current HCV transgenic models

Hepatits C virus (HCV) is an enveloped virus with positive‐sense single‐stranded RNA genome that causes both acute and persistent infections associated with chronic hepatitis, cirrhosis and hepatocellular carcinoma, which needs fully functional human hepatocytes for its development. Due to the strict human tropism of HCV, only human and higher primates such as chimpanzees have been receptive to HCV infection and development, cognition about pathophysiololgy and host immune responses of HCV infection is limited by lacking of simple laboratory models of infection for a long time. During the past decade, gene transfer approaches have been helpful to the understanding of the molecular basis of human disease. Transgenic cell lines, chimeric and transgenic animal models were developed and had been demonstrated their invaluable benefits. This review focuses on the existing HCV transgenic models and summarize the relative results about probable pathophysical changes induced by HCV proteins.     

Animal models for studying hepatitis C and alcohol effects on liver

Chronic consumption of ethanol has a dramatic effect on the clinical outcome of patients with hepatitis C virus (HCV) infection, but the mechanism linking these two pathologies is unknown. Presently, in vitro systems are limited in their ability to study the interaction between a productive wild-type HCV infection and chronic ethanol exposure. Mouse models are potentially very useful in dissecting elements of the HCV-ethanol relationship. Experiments in mice that transgenically express HCV proteins are outl...     

HCV实验动物模型研究进展

HCV是威胁人类健康的重要病原体之一,可在人体肝脏形成持续性感染,导致慢性肝炎、肝纤维化、肝硬化和肝癌。HCV的实验动物模型不仅是HCV免疫学、病理学和病毒学等基础科学的重要研究手段,还为HCV疫苗和药物的研发提供了关键的工具和平台。黑猩猩是除了人类以外唯一可以被HCV感染的灵长类动物,为HCV的研究做出了重要贡献,但其使用受到了成本及伦理上的限制。近年在利用树鼩和人源化小鼠建立HCV小动物模型的研究上取得良好的进展。本文将总结常用HCV实验动物模型的现状和挑战。     

丙型肝炎病毒小鼠实验模型的研究进展

丙型肝炎病毒（HCV）感染是导致慢性肝病的主要原因。大部分HCV感染者呈持续性感染,这与肝硬化和肝细胞癌紧密相关。近十年来,许多学者通过不懈的努力建立了各种行之有效的小鼠实验模型,基于这些模型的研究极大地丰富和加深了对HCV感染、致病、免疫等方面分子机理的认识,同时也极大地促进了新的抗病毒策略和特异药物筛选的发展。本文就目前最常见和未来有应用前景的两类小鼠实验模型作一综述。     

Animal models in the study of hepatitis C virus-associated liver pathologies

It is estimated that more than 170 million individuals worldwide are chronically infected with hepatitis C virus (HCV), with approximately 20% of the cases developing cirrhosis. Each year, between 1 and 4% of patients exhibiting cirrhosis develop hepatocellular carcinoma. Chronic HCV infection is also linked with the development of several metabolic disorders, including hepatic steatosis and insulin resistance. Research into HCV-related pathologies is hampered by a relative paucity of small animal models. As a result, little is known about the molecular mechanisms involved, and much of our current knowledge is drawn by inference from in vitro studies using overexpressed proteins. In this article, we will review the currently available animal models for the study of HCV pathogenesis, with an emphasis on murine models. Then, we will provide an overview of how these models have contributed to the deciphering of the molecular mechanisms underlying dysregulated lipid metabolism and hepatocellular carcinoma during HCV infection.     

In vitro replication models for the hepatitis C virus

Soon after the discovery of the hepatitis C virus (HCV), attention turned to the development of models whereby replication of the virus could be investigated. Among the HCV replication models developed, the HCV RNA replicon model and the newly discovered infectious cell culture systems have had an immediate impact on the study of HCV replication, and will continue to lead to important advances in our understanding of HCV replication. The aim of this study is to deal with developments in HCV replication models in a chronological order from the early 1990s to the recent infectious HCV cell culture systems.     

Biología molecular aplicada del virus de la hepatitis C

Since the discovery of the hepatitis C virus (HCV), a plethora of experimental models have evolved, allowing the virus's life cycle and the pathogenesis of associated liver diseases to be investigated. These models range from inoculation of cultured cells with serum from patients with hepatitis C to the use of surrogate models for the study of specific stages of the HCV life cycle: retroviral pseudoparticles for the study of HCV entry, replicons for the study of HCV replication, and the HCV cell culture model, which reproduces the entire life cycle (replication and production of infectious particles). The use of these tools has been and remains crucial to identify potential therapeutic targets in the different stages of the virus's life cycle and to screen new antiviral drugs. A clear example is the recent approval of two viral protease inhibitors (boceprevir and telaprevir) in combination with pegylated interferon and ribavirin for the treatment of chronic hepatitis C. This review analyzes the advances made in the molecular biology of HCV and highlights possible candidates as therapeutic targets for the treatment of HCV infection.     

Animal models for the study of hepatitis C virus infection and replication

Hepatitis C virus (HCV) hepatitis, initially termed non-A, non-B hepatitis, has become one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. With the help of animal models, our understanding of the virus has grown substantially from the time of initial discovery. There is a paucity of available animal models for the study of HCV, mainly because of the selective susceptibility limited to humans and primates. Recent work has focused modification of animals to permit HCV entry, replication and transmission. In this review, we highlight the currently available models for the study of HCV including chimpanzees, tupaia, mouse and rat models. Discussion will include methods of model design as well as the advantages and disadvantages of each model. Particular focus is dedicated to knowledge of pathophysiologic mechanisms of HCV infection that have been elucidated through animal studies. Research within animal models is critically important to establish a complete understanding of HCV infection, which will ultimately form the basis for future treatments and prevention of disease.     

Hepatitis C

The major cause of chronic post-transfusion hepatitis, the hepatitis C virus (HCV), has been identified. HCV is a single-stranded linear RNA virus with characteristics similar to the flaviviruses. A different agent, the hepatitis E virus, is associated with epidemic (enterically-transmitted) non-A, non-B hepatitis. At present, infection with HCV is recognized by the finding of anti-HCV antibodies, positive in up to 90% of patients with chronic non-A, non-B post-transfusion hepatitis. Antibodies to HCV are detected in 1% of normal volunteer blood donors and in the majority of donors implicated in post-transfusion hepatitis. HCV antibodies are also found in patients with autoimmune liver disease and hepatocellular carcinoma. Moreover, HCV infection may contribute to the pathogenesis of liver disease in alcoholic patients. The role of HCV infection in fulminant non-A, non-B hepatitis and hepatitis-associated aplastic anemia has not been elucidated as yet. Therapy of chronic non-A, non-B hepatitis with recombinant human alpha-interferon has been shown to improve or normalize aminotransferase levels in approximately 50% of patients, most of whom have evidence of HCV infection. However, relapse after cessation of treatment is common. In the future, screening blood for evidence of HCV infection may prevent most cases of non-A, non-B post-transfusion hepatitis.