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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034818-06
Application #
3172655
Study Section
Experimental Virology Study Section (EVR)
Project Start
1984-03-15
Project End
1992-01-31
Budget Start
1990-02-01
Budget End
1992-01-31
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Price, P M; Banerjee, R; Jeffrey, A M et al. (1992) The mechanism of inhibition of hepatitis B virus replication by the carbocyclic analog of 2'-deoxyguanosine. Hepatology 16:8-12
Bauer, J; Lengyel, G; Thung, S N et al. (1991) Human fetal hepatocytes respond to inflammatory mediators and excrete bile. Hepatology 13:1131-41
Zhai, W R; Vajta, G; Acs, G et al. (1990) A nude mouse model for the in vivo production of hepatitis B virus. Gastroenterology 98:470-7
Banerjee, R; Price, P M; Sung, M W et al. (1990) Selective inhibition of hepatitis B virus and human immunodeficiency virus sequence-promoted gene expression by cotransfected poly(I):poly(C). Virology 179:410-5
Price, P M; Banerjee, R; Acs, G (1989) Inhibition of the replication of hepatitis B virus by the carbocyclic analogue of 2'-deoxyguanosine. Proc Natl Acad Sci U S A 86:8541-4
Price, P M; Reichelderfer, C F; Johansson, B E et al. (1989) Complementation of recombinant baculoviruses by coinfection with wild-type virus facilitates production in insect larvae of antigenic proteins of hepatitis B virus and influenza virus. Proc Natl Acad Sci U S A 86:1453-6
Banerjee, R; Karpen, S; Siekevitz, M et al. (1989) Tumor necrosis factor-alpha induces a kappa B sequence-specific DNA-binding protein in human hepatoblastoma HepG2 cells. Hepatology 10:1008-13
Price, P M; Mohamad, A; Zelent, A et al. (1988) Translational selection in the expression of the hepatitis B virus envelope proteins. DNA 7:417-22
Sells, M A; Zelent, A Z; Shvartsman, M et al. (1988) Replicative intermediates of hepatitis B virus in HepG2 cells that produce infectious virions. J Virol 62:2836-44
Gerber, M A; Sells, M A; Chen, M L et al. (1988) Morphologic, immunohistochemical, and ultrastructural studies of the production of hepatitis B virus in vitro. Lab Invest 59:173-80

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