Hepatitis B virus(HBV) is a member of the hepadnavirus family.Hepadnaviruses can be found in both mammals(orthohepadnaviruses) and birds(avihepadnaviruses).The genetic variability of HBV is very high.There are eight g...Hepatitis B virus(HBV) is a member of the hepadnavirus family.Hepadnaviruses can be found in both mammals(orthohepadnaviruses) and birds(avihepadnaviruses).The genetic variability of HBV is very high.There are eight genotypes of HBV and three clades of HBV isolates from apes that appear to be additional genotypes of HBV.Most genotypes are now divided into subgenotypes with distinct virological and epidemiological properties.In addition,recombination among HBV genotypes increases the variability of HBV.This review summarises current knowledge of the epidemiology of genetic variability in hepadnaviruses and,due to rapid progress in the field,updates several recent reviews on HBV genotypes and subgenotypes.展开更多
AIM： Hepatitis B virus protein X （HBx） has been shown to be weakly oncogenic in vitro. The transforming activities of HBx have been linked with the inhibition of several functions of the tumor suppressor p53. We ha...AIM： Hepatitis B virus protein X （HBx） has been shown to be weakly oncogenic in vitro. The transforming activities of HBx have been linked with the inhibition of several functions of the tumor suppressor p53. We have studied whether HBx may have different effects on p53 depending on the cell type. METHODS： We used the human hepatoma cell line HepG2 and the immortalized murine hepatocyte line AML12 and analyzed stably transfected clones which expressed physiological amounts of HBx. P53 was induced by UV irradiation.RESULTS： The p53 induction by UV irradiation was unaffected by stable expression of HBx. However, the expression of the cyclin kinase inhibitor p21^waf/cip/sdi which gets activated by p53 was affected in the HBx transformed cell line AML12-HBx9, but not in HepG2. In AML-HBx9 cells, p21^waf/ciP/sdi -protein expression and p21^waf/dip/sdi transcription were deregulated. Furthermore, the process of apoptosis was affected in opposite ways in the two cell lines investigated. While stable expression of HBx enhanced apoptosis induced by UV irradiation in HepG2-cells, apoptosis was decreased in HBx transformed AML12-HBx9. P53 repressed transcription from the HBV enhancer I, when expressed from expression vectors or after induction of endogenous p53 by UV irradiation. Repression by endogenous p53 was partially reversible by stably expressed HBx in both cell lines.CONCLUSION： Stable expression of HBx leads to deregulation of apoptosis induced by UV irradiation depending on the cell line used. In an immortalized hepatocyte line HBx acted anti-apoptotic whereas expression in a carcinoma derived hepatocyte line HBx enhanced apoptosis.展开更多
AIM: To study the expression of HBV enhancer Ⅱ by transcription factor COUP-TF1. METHODS: In order to study the regulation of HBV variants in the vicinity of the NRRE we cloned luciferase constructs containing the HB...AIM: To study the expression of HBV enhancer Ⅱ by transcription factor COUP-TF1. METHODS: In order to study the regulation of HBV variants in the vicinity of the NRRE we cloned luciferase constructs containing the HBV enhancer Ⅱ from variants and from HBV genotypes A and D and cotransfected them together with expression vectors for COUP-TF1 into HepG2 cells. RESULTS: Our fi ndings show that enhancer Ⅱ of HBV genotype A is also repressed by COUP-TF1. In contrast, two different enhancer Ⅱ constructs of HBV genotype D were activated by COUP-TF1. The activation was independent of the NRRE because a natural variant with a deletion of nt 1763-1770 was still activated by COUP- TF1. CONCLUSION: Regulation of transcription of the HBV genome seems to differ among HBV genomes derived from different genotypes. These differences in transcriptional control among HBV genotypes may be the molecular basis for differences in the clinical course among HBV genotypes.展开更多
文摘Hepatitis B virus(HBV) is a member of the hepadnavirus family.Hepadnaviruses can be found in both mammals(orthohepadnaviruses) and birds(avihepadnaviruses).The genetic variability of HBV is very high.There are eight genotypes of HBV and three clades of HBV isolates from apes that appear to be additional genotypes of HBV.Most genotypes are now divided into subgenotypes with distinct virological and epidemiological properties.In addition,recombination among HBV genotypes increases the variability of HBV.This review summarises current knowledge of the epidemiology of genetic variability in hepadnaviruses and,due to rapid progress in the field,updates several recent reviews on HBV genotypes and subgenotypes.
基金grant 01 KI 9552 of the Bundesministerium fur Forschung und Technologie grant 01 KI 98589 of the Bundesministerium fur Bildung und Forschung to S.S. and W.H.G grant 10-1854-Scha I from Deutsche Krebshilfe to SS
文摘AIM： Hepatitis B virus protein X （HBx） has been shown to be weakly oncogenic in vitro. The transforming activities of HBx have been linked with the inhibition of several functions of the tumor suppressor p53. We have studied whether HBx may have different effects on p53 depending on the cell type. METHODS： We used the human hepatoma cell line HepG2 and the immortalized murine hepatocyte line AML12 and analyzed stably transfected clones which expressed physiological amounts of HBx. P53 was induced by UV irradiation.RESULTS： The p53 induction by UV irradiation was unaffected by stable expression of HBx. However, the expression of the cyclin kinase inhibitor p21^waf/cip/sdi which gets activated by p53 was affected in the HBx transformed cell line AML12-HBx9, but not in HepG2. In AML-HBx9 cells, p21^waf/ciP/sdi -protein expression and p21^waf/dip/sdi transcription were deregulated. Furthermore, the process of apoptosis was affected in opposite ways in the two cell lines investigated. While stable expression of HBx enhanced apoptosis induced by UV irradiation in HepG2-cells, apoptosis was decreased in HBx transformed AML12-HBx9. P53 repressed transcription from the HBV enhancer I, when expressed from expression vectors or after induction of endogenous p53 by UV irradiation. Repression by endogenous p53 was partially reversible by stably expressed HBx in both cell lines.CONCLUSION： Stable expression of HBx leads to deregulation of apoptosis induced by UV irradiation depending on the cell line used. In an immortalized hepatocyte line HBx acted anti-apoptotic whereas expression in a carcinoma derived hepatocyte line HBx enhanced apoptosis.
基金Supported by grant 10-1854-Scha I from Deutsche Krebshilfe, grant Scha778/2-1 from DFG to S.S. and Graduiertenkolleg Nu-cleoprotein complexes to S.S. and W.H.G.
文摘AIM: To study the expression of HBV enhancer Ⅱ by transcription factor COUP-TF1. METHODS: In order to study the regulation of HBV variants in the vicinity of the NRRE we cloned luciferase constructs containing the HBV enhancer Ⅱ from variants and from HBV genotypes A and D and cotransfected them together with expression vectors for COUP-TF1 into HepG2 cells. RESULTS: Our fi ndings show that enhancer Ⅱ of HBV genotype A is also repressed by COUP-TF1. In contrast, two different enhancer Ⅱ constructs of HBV genotype D were activated by COUP-TF1. The activation was independent of the NRRE because a natural variant with a deletion of nt 1763-1770 was still activated by COUP- TF1. CONCLUSION: Regulation of transcription of the HBV genome seems to differ among HBV genomes derived from different genotypes. These differences in transcriptional control among HBV genotypes may be the molecular basis for differences in the clinical course among HBV genotypes.
