Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Hartwig, D; Schütte, C; Warnecke, J; Dorn, I; Hennig, H; Kirchner, H; Schlenke, P.
The large form of ADAR 1 is responsible for enhanced hepatitis delta virus RNA editing in interferon-alpha-stimulated host cells.
J Viral Hepat. 2006; 13(3):150-157
Doi: 10.1111/j.1365-2893.2005.00663.x
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Dorn Isabel
- Schlenke Peter
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- Abstract:
- Hepatitis delta virus (HDV) RNA editing controls the formation of hepatitis-delta-antigen-S and -L and therefore indirectly regulates HDV replication. Editing is thought to be catalysed by the adenosine deaminase acting on RNA1 (ADAR1) of which two different forms exist, interferon (IFN)-alpha-inducible ADAR1-L and constitutively expressed ADAR1-S. ADAR1-L is hypothesized to be a part of the innate cellular immune system, responsible for deaminating adenosines in viral dsRNAs. We examined the influence of both forms on HDV RNA editing in IFN-alpha-stimulated and unstimulated hepatoma cells. For gene silencing, an antisense oligodeoxyribonucleotide against a common sequence of both forms of ADAR1 and another one specific for ADAR1-L alone were used. IFN-alpha treatment of host cells led to approximately twofold increase of RNA editing compared with unstimulated controls. If ADAR1-L expression was inhibited, this substantial increase in editing could no longer be observed. In unstimulated cells, ADAR1-L suppression had only minor effects on editing. Inhibition of both forms of ADAR1 simultaneously led to a substantial decrease of edited RNA independently of IFN-alpha-stimulation. In conclusion, the two forms of ADAR1 are responsible almost alone for HDV editing. In unstimulated cells, ADAR1-S is the main editing activity. The increase of edited RNA under IFN-alpha-stimulation is because of induction of ADAR1-L, showing for the first time that this IFN-inducible protein is involved in the base modification of replicating HDV RNA. Thus, induction of ADAR1-L may at least partially cause the antiviral effect of IFN-alpha in natural immune response to HDV as well as in case of therapeutic administration of IFN.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenosine Deaminase - physiology
- Carcinoma, Hepatocellular -
- Cell Line, Tumor -
- Electrophoresis, Polyacrylamide Gel -
- Gene Silencing -
- Hepatitis Delta Virus - genetics
- Hepatitis Delta Virus - immunology
- Hepatitis Delta Virus - physiology
- Humans -
- Immunoblotting -
- Interferon-alpha - immunology
- Oligoribonucleotides, Antisense - pharmacology
- RNA Editing - physiology
- RNA, Messenger - analysis
- RNA, Viral - metabolism
- RNA-Binding Proteins -
- Reverse Transcriptase Polymerase Chain Reaction -
- Find related publications in this database (Keywords)
- adenosine deaminase acting on RNA 1
- editing
- hepatitis delta virus
- interferon-alpha