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Molecular Therapy and Prevention of Liver Diseases

Hubert E. Blum

2008, 23(2): 81 doi: 10.1007/s12250-008-2953-8

Molecular analyses have become an integral part of biomedical research as well as clinical medicine. The definition of the genetic basis of many human diseases has led to a better understanding of their pathogenesis and has in addition offered new perspectives for their diagnosis, therapy and prevention. Genetically, human diseases can be classified as hereditary monogenic, acquired monogenic and polygenic diseases. Based on this classification, gene therapy is based on six concepts: (1) gene repair, (2) gene substitution, (3) cell therapy, (4) block of gene expression or function, (5) DNA vaccination and (6) gene augmentation. While major advances have been made in all areas of gene therapy during the last years, various delivery, targeting and safety issues need to be addressed before these strategies will enter clinical practice. Nevertheless, gene therapy will eventually become part of the management of patients with various liver diseases, complementing or replacing existing therapeutic and preventive strategies.


林菊生, 高琳琳Ju-sheng LIN *

2008, 23(2): 93 doi: 10.1007/s12250-008-2939-6

Since HBV DNA integration was discovered for the first time in 1980, various methods have been used to detect and study it, such as Southern Blot, in situ hybridization, polymerase chain reaction and so on. HBV DNA integration is thought to be random on the whole although some hot spots of integration were described by some researchers, one of which might be the repetitive sequences of the genomic DNA. Besides, DNA damage, especially double-strand breaks could promote HBV DNA integration into host genome. HBV DNA integration into cells may damage the stability of the genome, cause DNA rearrangement, promote DNA deletion and induce the formation of HCC.

自从1980年首次发现乙肝病毒DNA整合,用来研究和检测的方法层出不穷,如Southern 印迹,原位杂交,聚合酶链式反应等。尽管某些科学家发现了一些乙肝病毒DNA的整合热点,如基因组的重复序列,但总体上来说这种整合是随机的。另外,DNA损伤,尤其是双链断裂可以促进乙肝病毒DNA整合入宿主基因。乙肝病毒DNA整合入宿主细胞可能会影响基因组的稳定性,引起DNA重排,促进DNA缺失并诱发肝细胞癌的形成。


徐飏, 石春薇, 张小勇, 裴荣娟, 陆蒙吉

2008, 23(2): 100 doi: 10.1007/s12250-008-2940-0


Recent Advances in Research on Hepadnaviral Infection in the Woodchuck Model*

Ina Schulte, juan ZHANG, ji MENG, juan PEI, Mengji LU, Michael Roggendorf

2008, 23(2): 107 doi: 10.1007/s12250-008-2941-z

The woodchuck model is an excellent animal model to study hepadnaviral infection. The new progresses in this model made possible to examine the T-cell mediated immune responses in acute and chronic hepadnaviral infection. Recently, a new assay for cytotoxic T-cells based on detection of CD107 was established for the woodchuck model. In addition, new immunotherapeutic approaches based on combination of potent antiviral treatment and DNA-protein vaccines were proven to be useful for treatment of chronic hepatitis B.

The Role of the Innate Immune System of the Liver in the Control of HBV and HCV*

Jun Wu, Ruth Br?ring, J?rg F. Schlaak*

2008, 23(2): 116 doi: 10.1007/s12250-008-2942-y

Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection are among the most frequent causes of chronic liver disease worldwide. As recent studies suggested that Toll like receptor (TLR)-based therapies may represent a promising approach in the treatment of HBV infection, we have studied the role of the local innate immune system of the liver as possible mediator of this effect. Murine non-parenchymal liver cells (NPC; Kupffer cells, KC; sinusoidal endothelial cells, LSEC) were isolated from C57/BL6 and stimulated by TLR 1-9 agonists. Supernatants were harvested and assayed for their antiviral activity against HBV in HBV-Met cells and HCV in the murine HCV replicon cell line MH1. Only supernatants from TLR 3 and -4 stimulated KC and TLR 3 stimulated LSEC were able to potently suppress HBV and HCV replication. By using neutralizing antibodies we could demonstrate that the TLR 3- but not the TLR 4 mediated effect is exclusively mediated through IFN-β. Our data indicate that TLR 3 and -4 mediated stimulation of NPC leads to production of IFN-β which can potently suppress HBV and HCV replication. This is of relevance for the local control of viral hepatitis infection by the innate immune system of the liver, the development of novel TLR-based therapeutic approaches and sheds new light on the viral crosstalk between HCV (TLR 3 stimulator) and HBV.

Virus-host Interactions during Hepatitis C Virus Entry - Implications for Pathogenesis and Novel Treatment Approaches

Joachim Lupberger, Mirjam B, Anita Haberstroh, Eva K, Sophie Krieger, Eric Soulier, Christine Thumann, Cathy Royer, Samira Fafi-Kremer, Catherine Schuster, oise Stoll-Keller, Hubert E, and Thomas

2008, 23(2): 124 doi: 10.1007/s12250-008-2943-x

Hepatitis C virus (HCV) is a member of the Flaviviridae family and causes acute and chronic hepatitis. Chronic HCV infection may result in severe liver damage including liver cirrhosis and hepatocellular carcinoma. The liver is the primary target organ of HCV, and the hepatocyte is its primary target cell. Attachment of the virus to the cell surface followed by viral entry is the first step in a cascade of interactions between the virus and the target cell that is required for successful entry into the cell and initiation of infection. This step is an important determinant of tissue tropism and pathogenesis; it thus represents a major target for antiviral host cell responses, such as antibody-mediated virus neutralization. Following the development of novel cell culture models for HCV infection our understanding of the HCV entry process and mechanisms of virus neutralization has been markedly advanced. In this review we summarize recent developments in the molecular biology of viral entry and its impact on pathogenesis of HCV infection, development of novel preventive and therapeutic antiviral strategies.

The Role of Viral Mutation in the Pathogenesis of Chronic Viral Hepatitis

Yu-ming WANG *, Lin LIU

2008, 23(2): 132 doi: 10.1007/s12250-008-2944-9



王桂凤, 左建平,

2008, 23(2): 137 doi: 10.1007/s12250-008-2945-8



王适群, 吴建国

2008, 23(2): 146 doi: 10.1007/s12250-008-2952-9