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丙型肝炎病毒复制模型系统
0 引言丙型肝炎是严重威害人民生命健康的疾病之一,其慢性率高,肝硬化及原发性肝癌的发生率高.然而,迄今为止仍无令人满意的治疗手段,干扰素单用或联合用病毒唑治疗总体应答率比较低.阻碍人们对丙型肝炎病毒(HCV)深人研究的原因之一是缺乏一个能高效支持病毒复制的可靠的模型,近十几年来人们为寻找合适的模型进行了不懈的努力,取得了可喜的成就,现就这方面的研究成果综述如下[1-3].
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Small rodent models of hepatitis B and C virus replication and pathogenesis
The narrow host range of infection supporting the long-term propagation of hepatitis B and C viruses is a major limitation that has prevented a more thorough understanding of persistent infection and the pathogenesis of chronic liver disease (CLD).With hepatitis B virus (HBV),this has been partially overcome by the discovery and characterization of HBV-like viruses in wild animals.With hepatitis C virus (HCV),related Fiaviviruses have been used as surrogate systems for such studies.Independent work has developed various mouse strains for the transplantation of human hepatocytes,which are then susceptible to infection with HBV and HCV.Other laboratories have developed transgenic mice that express virus gene products and/or support virus replication.Some HBV transgenic mouse models develop fulminant hepatitis,acute hepatitis,or CLD following adoptive transfer,while others spontaneously develop hepatocellular carcinoma (HCC),as in human infections.Among HCV transgenic mice,most develop no disease,but acute hepatitis has been observed in one model,while HCC appears in another.Other mouse models include the introduction of xenographs that replicate HBV or HCV.Although mice are not susceptible to these viruses,their ability to support virus replication and to develop liver disease characteristic of human infections,provides new opportunities to study pathogenesis and develop novel therapeutics.
