All major types of interferon (IFN) efficiently inhibit hepatitis C virus (HCV) replication in vitro and in vivo. Remarkably, HCV replication is not sensitive to IFN in the hepatoma cell line Huh6, despite an intact signaling pathway. We performed transcriptome analyses between Huh6 and Huh-7 to identify effector genes of the IFN response and thereby identified the DExD/H box helicase DDX60L as a restriction factor of HCV replication. DDX60L and its homolog DDX60 were both induced upon viral infection and IFN treatment in primary human hepatocytes. However, exclusively DDX60L knockdown increased HCV replication in Huh-7 cells, and rescued HCV replication from type II IFN as well as type I and III IFN treatment, suggesting that DDX60L is an important effector protein of the innate immune response against HCV. DDX60L had no impact on replication of hepatitis A virus (HAV), but severely impaired production of lentiviral vectors, arguing for a potential antiretroviral activity. Detection of endogenous DDX60L protein turned out to be difficult due to instability. DDX60L knockdown did not alter interferon stimulated gene (ISG) induction after IFN treatment, suggesting that it is a direct effector of the innate immune response. It most likely inhibits viral RNA replication, since we found no impact of DDX60L on translation or stability of HCV subgenomic replicons, nor additional impact on entry and assembly of infectious virus. Similar to its homolog DDX60, DDX60L had a moderate impact on retinoic acid-inducible gene I (RIG-I)-dependent activation of innate immunity arguing for additional functions in the sensing of viral RNA.
DDX60L Is an Interferon-Stimulated Gene Product Restricting Hepatitis C Virus Replication in Cell Culture.
Cell line, Treatment
View SamplesThe arylhydrocarbon receptor is a ligand inducible transcription factor. Known to control xenobiotic metabolizing enzymes, it also affects - depending on the cell type - numerous other genes, either directly or indirectly. With respect to the immune system, persistent activation leads to immunosuppression. We asked how the AhR is involved in Langerhans cells. These antigen presenting cells of the skin are responsible for allergies against chemicals (thus xenobiotic metabolism might be relevant) and a recently detected endogenous ligand, FICZ made by UVB radiation from tryptophane, is particularly abundant in the skin.
Langerhans cell maturation and contact hypersensitivity are impaired in aryl hydrocarbon receptor-null mice.
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View SamplesThe transcriptome of murine LC after 24 hours in vivo exposure to a moderate dose of 10 microgram 2,3,7,8-tetrachlorodibenzo-p-dioxin was studied.
Langerhans cell maturation and contact hypersensitivity are impaired in aryl hydrocarbon receptor-null mice.
No sample metadata fields
View SamplesOver activation of the aryl hydrocarbon receptor (AhR) by TCDD results ampng other phenotypes in severe thymic atrophy accompanied by immunosuppression. The link between thymic atrophy, skewed thymocyte differntiation and immunosuppression is still not fully resolved. This study investigates the TCDD elicted exprssion changes in the ET, cortical thymus epithelial cell line.
Promoter analysis of TCDD-inducible genes in a thymic epithelial cell line indicates the potential for cell-specific transcription factor crosstalk in the AhR response.
Treatment, Time
View SamplesOver-activation of the aryl hydrocarbon receptor by TCDD in mice leads among other phenotypes to a severe thymic atrophy accompanied by immunosuppression. TCDD causes a block in thymocyte maturation and a preferential emigration of immature CD4-CD8- DN thymocytes (recent thymic emigrants) into the periphery. As part of this study gene expression profiles from DN thymocytes and thymic emigrants were generated from TCDD and solvent control mice
Role of the aryl hydrocarbon receptor in thymocyte emigration in vivo.
Specimen part, Treatment
View SamplesGlobal gene expression patterns were determined from microarray results on day 1, 3, 5, 7, 10 and 14 during plantaris muscle hypertrophy induced by synergist ablation in young adult mice (5 months).
Time course of gene expression during mouse skeletal muscle hypertrophy.
Sex, Age, Specimen part, Treatment, Time
View SamplesCD4+ T cells from 8-12 week female mice were isolated from wt and AhR-/- mice 24h after injection of 10g/kg TCDD or solvent control.
Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.
Sex, Treatment
View SamplesEffect of an immunosupressive dose of TCDD, a ligand for the aryl hydrocarbon receptor, on the gene expression profile of fetal DN thymocytes and thymic emigrants
Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.
Specimen part, Treatment
View Samples8-12 week, female C57BL/6 mice were injected with 10 g/kg TCDD or solvent control. CD8+ T cells from spleen were FACS purified and submitted to transcription profiling
Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.
Sex, Treatment
View SamplesEffect of the over activation of the aryl hydrocarbon receptor on gene expression of spleen derived dendritic cells.
Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.
Sex, Treatment
View Samples