Suri, D; Schilling, R; Lopes, AR; Mullerova, I; Colucci, G; Williams, R; Naoumov, NV; (2001) Non-cytolytic inhibition of hepatitis B virus replication in human hepatocytes. Journal of Hepatology , 35 (6) 790 - 797.
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BACKGROUND/AIMS: Interferon-gamma (IFN-gamma) has been shown to abolish hepatitis B virus (HBV) gene expression and replication in HBV transgenic mice without destroying infected hepatocytes. We investigated the characteristics of IFN-gamma induced non-cytolytic inhibition of viral replication in human HBV infection. METHODS: We used an in vitro model where lymphocytes from 15 HBsAg positive patients were co-cultured with transfected hepatocytes supporting HBV replication. The effector and target cells were separated by a membrane, which allowed transfer of soluble factors only, to determine whether IFN-gamma produced from antigen-specific CD4+ T cells or mitogen stimulated lymphocytes inhibits HBV replication. RESULTS: IFN- gamma produced following lymphocyte stimulation reduced cytoplasmic HBV DNA in the target cells. The degree of HBV DNA reduction correlated with the level of IFN-gamma in the supernatants. Further investigations using naturally infected human hepatocytes confirmed that recombinant IFN-gamma reduces HBV DNA and HBV RNA in these cells as well, in parallel with the induction of cellular interferon-responsive genes. This antiviral effect was without significant cytotoxicity and was more pronounced in hepatocytes from patients with low HBV replication. CONCLUSIONS: These results provide direct evidence that IFN-gamma can inhibit both HBV transcription and replication in human hepatocytes without cell lysis
|Title:||Non-cytolytic inhibition of hepatitis B virus replication in human hepatocytes|
|Additional information:||UI - 21602036 LA - eng RN - 0 (Antiviral Agents) RN - 0 (DNA, Viral) RN - 0 (RNA, Messenger) RN - 0 (RNA, Viral) RN - 82115-62-6 (Interferon Type II) PT - Journal Article DA - 20011212 IS - 0168-8278 SB - IM CY - Denmark|
|Keywords:||adult, AGENT, AGENTS, antagonists & inhibitors, antigen-specific, Antiviral Agents, As, CD4+, CD4+ T cells, cell, CELLS, Cells, Cultured, Cellular, characteristics, Coculture, cytotoxicity, Denmark, DNA, Dna, Viral, drug effects, EFFECTOR, expression, factors, gamma, GENE, Gene Expression, Gene Expression Regulation, GENE-EXPRESSION, Genes, HBV, HBV DNA, Hepatitis, hepatitis B, Hepatitis B Virus, hepatocyte, HEPATOCYTES, human hepatocyte, Human Hepatocytes, IFN gamma, IFN-GAMMA, IM, in vitro, In-vitro, INDUCTION, Infection, INHIBIT, inhibition, INTERFERON, Interferon gamma, Interferon Type II, INTERFERON-GAMMA, investigations, LA, LEVEL, Low, LYMPHOCYTE, Lymphocytes, lysis, membrane, MESSENGER, metabolism, Methods, mice, MITOGEN, model, Monocytes, Patient, patients, pharmacology, physiology, positive, POSITIVE PATIENTS, recombinant, REDUCTION, REPLICATION, Result, Rna, RNA, Messenger, Rna, Viral, Stimulation, Support, Non-U.S.Gov't, T cell, T CELLS, T-CELL, T-CELLS, target, Target Cell, TRANSCRIPTION, transfer, transgenic, transgenic mice, Type II, viral, VIRUS, Virus Replication, VITRO|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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