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REPLICATION AND ONCOGENICITY OF HBV

乙型肝炎病毒的复制和致癌性

基本信息

批准号：
3172655
负责人：
GEORGE ACS
金额：
$ 17.57万
依托单位：
MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-03-15 至 1992-01-31
项目状态：
已结题

项目摘要

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.

B型肝炎病毒（HBV）是一种主要的人类病原体，这可能导致肝硬化和肝细胞癌的发展 carcinoma. 持续感染发生在约2亿人，并与不同的组织类型，慢性肝病反映了不同水平的活性肝细胞损伤和炎症。在过去的几年里，积累了大量的信息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。复制周期和病理学，包括 HVB的致癌性，由于缺乏，无法阐明病毒在其中复制的组织培养系统。然而，在这方面，我们成功地从人源HEP G2细胞中分离出HEP G2细胞，肝母细胞瘤，HBV DNA。建立了细胞系从这些转染的细胞中，附加型HBV DNA，并支持完整的HBV复制。的这条线路的可用性将取消大部分的后勤目前遇到的问题。现在，在实验上，研究：a）激素、生长因子和抗病毒药物的作用药物的复制，以及使肝脏特异性反式- 参与复制周期的配体因子; B）免疫对这些细胞的反应，这些细胞积累在表面和核心抗原;和c）致癌或共- 乙型肝炎病毒对裸鼠的致癌作用在用致癌物或肿瘤促进剂治疗之前或之后。此外，还将通过以下方法研究HBV的致癌潜力：将HBV DNA转染到“永生化”的人肝细胞中通过用A转染人胎肝细胞获得的细胞系含有SV 40 DNA的质粒，在复制的

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Inhibition of the replication of hepatitis B virus by the carbocyclic analogue of 2'-deoxyguanosine.

DOI：
10.1073/pnas.86.21.8541
发表时间：
1989-11
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Peter M. Price;Ranjit Banerjee;George Acs
通讯作者：
Peter M. Price;Ranjit Banerjee;George Acs

Expression in Escherichia coli of a cloned DNA sequence encoding the pre-S2 region of hepatitis B virus.

编码乙型肝炎病毒前 S2 区的克隆 DNA 序列在大肠杆菌中的表达。

DOI：
10.1073/pnas.82.22.7540
发表时间：
1985
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Offensperger,W;Wahl,S;Neurath,AR;Price,P;Strick,N;Kent,SB;Christman,JK;Acs,G
通讯作者：
Acs,G

A nude mouse model for the in vivo production of hepatitis B virus.

用于体内产生乙型肝炎病毒的裸鼠模型。