The Molecular Biology of the Hepatitis B Viruses

Ganem, Don; Varmus, Harold

doi:10.1146/annurev.bi.56.070187.003251

Cited by 1,014 publications

(611 citation statements)

References 97 publications

Supporting

Mentioning

595

Contrasting

Unclassified

Order By: Relevance

“…The polymerase protein contains a viral RNA packaging signal and performs multiple enzymatic functions including reverse transcriptase, DNA polymerase, and RNase H activity that are essential for viral replication. 15 The core protein, known as hepatitis B core antigen (HBcAg), rapidly forms homodimers that self-assemble into capsid particles 16 in the cytoplasm and the nucleus of the hepatocyte. The intranuclear capsid particles appear to be empty, and their role in the viral life cycle is not understood.…”

Section: The Virus and Its Life Cyclementioning

confidence: 99%

Viruses, Immunity, and Cancer: Lessons from Hepatitis B

Chisari

2000

The American Journal of Pathology

281

226

View full text Add to dashboard Cite

show abstract

Section: The Virus and Its Life Cyclementioning

confidence: 99%

Viruses, Immunity, and Cancer: Lessons from Hepatitis B

Chisari

2000

The American Journal of Pathology

281

226

View full text Add to dashboard Cite

show abstract

“…For adoptive immunotherapy using HBx-specific CTLs, we generated CTL clones restricted to the HBx 52-60 or HBx 115-123 peptide using a limiting dilution technique. LC-46, an HBx 52-60-specific clone, is CD62L ؊ CD69 ؉ CD45RO ؉ CD45RA ؊ CD25 dim and is stained by IFN-␥ (ϳ92%) H epatitis B viruses (HBV) 2 are small hepatotropic pararetroviruses that replicate by reverse transcription and establish persistent liver infection in humans and other animals (1,2). HBV are strongly associated with the development of primary liver cancer (hepatocellular carcinoma (HCC)), which is one of the most prevalent forms of human cancer worldwide (1).…”

Section: Tumor Eradication By Hepatitis B Virus X Antigen-specific Cdmentioning

confidence: 99%

Tumor Eradication by Hepatitis B Virus X Antigen-Specific CD8+ T Cells in Xenografted Nude Mice

Chun¹,

Lee²,

Cheong³

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

We have previously reported several CTL epitopes derived from the hepatitis B viral X Ag (HBx). In this study, we evaluated whether HBx-specific CTLs can be effectively used in adoptive cancer immunotherapy. To validate the possibility, four peptides containing a HLA-A2.1-restricted binding consensus motif were identified from the HBx protein and tested for their ability to activate CTL from PBMCs isolated from chronic carriers of HBV (n = 12). We selected two highly potent epitopes, HBx 52–60 (HLSLRGLFV) and HBx 115–123 (CLFKDWEEL), that are capable of inducing Ag-specific cytotoxic T cells in patient PBMCs. For adoptive immunotherapy using HBx-specific CTLs, we generated CTL clones restricted to the HBx 52–60 or HBx 115–123 peptide using a limiting dilution technique. LC-46, an HBx 52–60-specific clone, is CD62L−CD69+CD45RO+CD45RA−CD25dim and is stained by IFN-γ (∼92%), IL-2 (30%), and TNF-α (56%), but not by IL-5, IL-10, IL-12, or TNF-β, indicating that the cells are fully activated T cytotoxic 1-type cells. When LC-46 cells were adoptively transferred into xenografted nude mice bearing human hepatomas expressing HLA-A2.1 molecules and intracellular HBx proteins, the tumors were eradicated. Taken together, our data provide solid evidence for the feasibility of adoptive immunotherapy with HBx-sensitized CTLs in hepatitis disease, including hepatocellular carcinoma (HCC).

show abstract

“…HBV is the smallest human DNA virus, with a genome of 3,200 base pairs, and belongs to the family Hepadnaviridae [2]. The partially double-stranded circular DNA encodes four overlapping open reading frames including surface (S), core (C), polymerase (P), and X genes [3] (Fig.…”

Section: Introductionmentioning

confidence: 99%

Role of viral factors in the natural course and therapy of chronic hepatitis B

Kao

2007

Hepatol Int

View full text Add to dashboard Cite

Hepatitis B virus (HBV) infection is a global health problem that causes a wide spectrum of liver disease, including acute or fulminant hepatitis, inactive carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of hepatocyte damage associated with HBV is mainly through immune-mediated mechanisms. On the basis of the virus and host interactions, the natural history of HBV carriers who are infected in early life can be divided into four dynamic phases. The frequency, extent, and severity of hepatitis flares or acute exacerbation in the second immune clearance and/or fourth reactivation phase predict liver disease progression in HBV carriers. In the past decade, hepatitis B viral factors including serum HBV DNA level, genotype, and naturally occurring mutants predictive of clinical outcomes have been identified. The higher the serum HBV DNA level after the immune clearance phase, the higher the incidence of adverse outcomes over time. In addition, high viral load, genotype C, basal core promoter mutation, and pre-S deletion correlate with increased risk of cirrhosis and HCC development. As to the treatment of chronic hepatitis B, patients with high HBV DNA level and genotype C or D infection are shown to have a worse response to interferon therapy. In conclusion, serum HBV DNA level, genotype, and naturally occurring mutants are identified to influence liver disease progression and therapy of chronic hepatitis B. More investigations are needed to clarify the molecular mechanisms of the viral factors involved in the pathogenesis of each stage of liver disease and the response to antiviral treatments.

show abstract

The Molecular Biology of the Hepatitis B Viruses

Cited by 1,014 publications

References 97 publications

Viruses, Immunity, and Cancer: Lessons from Hepatitis B

Viruses, Immunity, and Cancer: Lessons from Hepatitis B

Tumor Eradication by Hepatitis B Virus X Antigen-Specific CD8+ T Cells in Xenografted Nude Mice

Role of viral factors in the natural course and therapy of chronic hepatitis B

Contact Info

Product

Resources

About