REPLICATION AND ONCOGENICITY OF HBV

乙肝病毒(乙肝)是人类的主要病原体，感染 可导致肝硬变和肝细胞癌的发展 癌症。持续性感染发生在大约2亿人中 它与不同的组织学类型的 反映不同活跃程度的慢性肝病 肝细胞损伤和炎症。在过去的几年里， 与结构相关的信息量已经积累起来 病毒粒子的遗传组织和复制 病毒，以及病毒基因的转录和翻译。 复制循环以及病理生物学，包括 HVB的致癌性，因缺乏而无法阐明 病毒在其中复制的组织培养系统。然而， 我们成功地将来源于人类的Hep G2细胞 肝母细胞瘤，带有HBVDNA。建立了一株细胞系 从这些转基因细胞中获得整合的和 异构体的HBVDNA，支持完整的HBVDNA复制。这个 这条线路的可用性应该会取消大部分的物流 到目前为止遇到的问题。现在在实验上是可行的 研究：a)激素、生长因子和抗病毒药物的作用 复制上的试剂以及鉴定肝脏特异性反式- 复制周期中涉及的免疫因子；b)免疫 对这些细胞的反应，这些细胞既积累表面又积累核心 膜上的抗原；以及c)致癌或共同致癌的 乙肝病毒裸鼠体内注射细胞致癌作用的研究 在使用致癌物或促癌剂治疗之前或之后。 此外，还将通过以下方式研究乙肝病毒的致癌潜力 将HBVDNA导入永生化的人肝细胞 人胎肝细胞转染法获得的细胞系 含有SV40 DNA的质粒在起始处发生突变 复制。

Hepatitis B virus (HBV) is a major human pathogen, infection with which can lead to the development of cirrhosis and hepatocellular carcinoma. Persistant infection occurs in about 200 million people and is associated with different histological types of chronic liver disease reflecting varying levels of active hepatocyte damage and inflammation. In the last few years, vast amounts of information has accumulated relative to the structure of the virion, the genetic organization and replication of the virus, as well as the transcription and translation of viraal genes. The replicative cycle as well as the pathobiology, including the oncogenicity of HVB, could not be elucidated due to the absence of a tissue culture system in which the virus replicates. However, we succeeded in transfecting HEP G2 cells, derived from a human hepatoblastoma, with HBV DNA. A cell lines was established from these transfected cells which contains integrated and episomal HBV DNA and supports complete HBV replication. The availability of this line should abolish most of the logistic problems encountered so far. It is now experimentally feasible to study: a) the effect of hormones, growth factors, and antiviral agents on the replicaton as well as to idenify liver specific trans- cating factors involved in the replicative cycle; b) the immune response to these cells, which accumulate both surface and core antigens on their membranes; and c) the carcinogenic or co- carcinogenic effect of HBV by injecting these cells into nude mice before or after treatment with carcinogens, or tumor promoters. In addition, the oncogenic potential of HBV will be also studied by transfecting HBV DNA into an "immortalized" human liver cell line obtained by transfecting fetal human liver cells with a plasmid containing SV40 DNA mutated at the origin of replication.