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Hepatitis B Virus Replication (hepatitis + b_virus_replication)
Selected AbstractsInterferon-inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication,HEPATOLOGY, Issue 6 2006Marianne Bonvin Hypermutations in hepatitis B virus (HBV) DNA by APOBEC3 cytidine deaminases have been detected in vitro and in vivo, and APOBEC3G (A3G) and APOBEC3F (A3F) have been shown to inhibit the replication of HBV in vitro, but the presumably low or even absent hepatic expression of these enzymes has raised the question as to their physiological impact on HBV replication. We show that normal human liver expresses the mRNAs of APOBEC3B (A3B), APOBEC3C (A3C), A3F, and A3G. In primary human hepatocytes, interferon alpha (IFN-,) stimulated the expression of these cytidine deaminases up to 14-fold, and the mRNAs of A3G, A3F, and A3B reached expression levels of 10%, 3%, and 3%, respectively, relative to GAPDH mRNA abundance. On transfection, the full-length protein A3BL inhibited HBV replication in vitro as efficiently as A3G or A3F, whereas the truncated splice variant A3BS and A3C had no effect. A3BL and A3BS were detected predominantly in the nucleus of uninfected cells; however, in HBV-expressing cells both proteins were found also in the cytoplasm and were associated with HBV viral particles, similarly to A3G and A3F. Moreover, A3G, A3F, and A3BL, but not A3BS, induced extensive G-to-A hypermutations in a fraction of the replicated HBV genomes. In conclusion, the editing enzymes A3BL, A3F, and most markedly A3G, which are expressed in liver and up-regulated by IFN-, in hepatocytes, are candidates to contribute to the noncytolytic clearance of HBV. (HEPATOLOGY 2006;43:1364,1374.) [source] The correlation of hepatocyte nuclear factor 4 alpha and 3 beta with hepatitis B virus replication in the liver of chronic hepatitis B patientsJOURNAL OF VIRAL HEPATITIS, Issue 8 2009Y. Long Summary., Hepatocyte nuclear factors 4 alpha (HNF4,) and 3 beta (HNF3,) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV). Using cell culture and animal models, we showed that HNF4, supports HBV replication in nonhepatic cells and HNF3, inhibits HBV replication. However, the expression of HNF4, and HNF3, in the liver tissue of chronic HBV-infected patients and the relationship between the levels of HNF4, and HNF3, and HBV replication are unclear. In this study, liver biopsy specimens from 86 chronic HBV-infected patients were collected. The expression levels of HNF4,, HNF3,, hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) were detected by an immunohistochemical technique and the level of HBV DNA was checked by in situ hybridization with serial sections from liver biopsy tissue samples. We show here that samples with higher levels of HNF4, expression also have higher levels of HBsAg, HBcAg and HBV DNA. In contrast, in samples with higher levels of HNF3, expression, levels of HBsAg, HBcAg and HBV DNA were lower. There was a positive correlation between HNF4, expression and HBV replication, and a negative correlation between HNF3, expression and HBV replication, in the liver of chronic HBV-infected patients. This suggests that HNF4, and HNF3, likely participate in HBV replication in patients with HBV infection, or that HBV replication may somehow influence the expression of HNF4, and HNF3, in the liver. [source] Suppression of p38 mitogen-activated protein kinase inhibits hepatitis B virus replication in human hepatoma cell: the antiviral role of nitric oxideJOURNAL OF VIRAL HEPATITIS, Issue 7 2008W.-W. Chang Summary., The role of the p38 mitogen-activated protein kinase (MAPK) pathway in hepatitis B virus (HBV) replication was investigated in this study. After transient transfection with HBV plasmid, p38 MAPK, but not JNK or ERK1/2, was significantly phosphorylated in human hepatoma cell Huh7. Interestingly, HBV proteins and RNA synthesis were significantly inhibited by a specific inhibitor of p38 MAPK, SB203580, in a dose-dependent manner. Intracellular core-associated DNA, extracellular virion-associated DNA and covalently closed circular DNA were also significantly inhibited by SB203580. Further results showed the antiviral role of nitric oxide (NO) on the suppression of HBV replication and downregulation of p38 MAPK phosphorylation. In conclusion, these results suggested that suppression of phosphorylation of p38 MAPK by inhibitor or NO could inhibit intracellular HBV replication. [source] Inhibition of hepatitis B virus replication in 2.2.15 cells by expressed shRNAJOURNAL OF VIRAL HEPATITIS, Issue 3 2005X.-R. Ren Summary., Hepatitis B virus (HBV) infection is a worldwide health problem. To determine whether RNA interference (RNAi) could inhibit ongoing HBV replication in 2.2.15 cells, we constructed shRNA-producing vector pU6P based on the mouse U6 RNA promoter and cloned 12 targeted sequences against HBV into the vector, resulting in a series of pU6-siHBV vectors. The recombinant vectors were transfected into 2.2.15 cells, HBsAg and HBeAg in cultured media were assayed using enzyme-linked immunosorbent assay at various days after transfection. The amount of HBV DNA in the culture medium was quantitated by real-time polymerase chain reaction. HBsAg and HBeAg expression were inhibited by 72.8 ± 5.4% (P = 0.00003) and 55.8 ± 6.2% (P = 0.000026), respectively, 4 days after transfection with pU6-siHBV5. The greatest inhibition of HBV DNA was decreased by approximately 1.9-fold (P = 0.013) on day 6 post transfection with pU6-siHBV11 compared with that of empty vector. No change was found for HBV protein expression and DNA replication on pU6-siGFP (negative control) transfected cells. Our data demonstrate that the transfection of HBV-targeted shRNA-producing vector in 2.2.15 cells could inhibit the HBV protein expression and HBV DNA replication specifically. RNAi may be considered as a potential antiviral approach for human HBV infection. [source] Review article: nucleoside analogues for the treatment of chronic hepatitis BALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2004H. M. Younger Summary Current accepted treatment for chronic hepatitis B uses either the immunomodulator interferon alpha or nucleoside analogues lamivudine or adefovir. Interferon has side effects which mean it is often poorly tolerated. Long-term use of lamivudine is associated with increasing viral resistance for each year it is taken and the rebound viraemia that can occur when the drug is stopped is also of concern to many. Adefovir appears to have less of the resistance issues of lamivudine but is still a relatively new drug and at present its use is principally limited to patients with lamivudine-resistant disease. A number of other nucleoside analogues are currently being developed with some now at the stage of early clinical trials. A proportion share the significant resistance problems of lamivudine but many appear to have more potent anti-viral effect than the drugs currently available. If some of these newer anti-viral agents are approved for use in chronic hepatitis B, the potential for prolonged suppression of hepatitis B virus replication with resultant stabilization or improvement in liver disease may be achieved. [source] | ||||||||||