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  • 1
    Publication Date: 2014-02-22
    Description: Current antiviral agents can control but not eliminate hepatitis B virus (HBV), because HBV establishes a stable nuclear covalently closed circular DNA (cccDNA). Interferon-alpha treatment can clear HBV but is limited by systemic side effects. We describe how interferon-alpha can induce specific degradation of the nuclear viral DNA without hepatotoxicity and propose lymphotoxin-beta receptor activation as a therapeutic alternative. Interferon-alpha and lymphotoxin-beta receptor activation up-regulated APOBEC3A and APOBEC3B cytidine deaminases, respectively, in HBV-infected cells, primary hepatocytes, and human liver needle biopsies. HBV core protein mediated the interaction with nuclear cccDNA, resulting in cytidine deamination, apurinic/apyrimidinic site formation, and finally cccDNA degradation that prevented HBV reactivation. Genomic DNA was not affected. Thus, inducing nuclear deaminases-for example, by lymphotoxin-beta receptor activation-allows the development of new therapeutics that, in combination with existing antivirals, may cure hepatitis B.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lucifora, Julie -- Xia, Yuchen -- Reisinger, Florian -- Zhang, Ke -- Stadler, Daniela -- Cheng, Xiaoming -- Sprinzl, Martin F -- Koppensteiner, Herwig -- Makowska, Zuzanna -- Volz, Tassilo -- Remouchamps, Caroline -- Chou, Wen-Min -- Thasler, Wolfgang E -- Huser, Norbert -- Durantel, David -- Liang, T Jake -- Munk, Carsten -- Heim, Markus H -- Browning, Jeffrey L -- Dejardin, Emmanuel -- Dandri, Maura -- Schindler, Michael -- Heikenwalder, Mathias -- Protzer, Ulrike -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1221-8. doi: 10.1126/science.1243462. Epub 2014 Feb 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Virology, Technische Universitat Munchen-Helmholtz Zentrum Munchen, 81675 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24557838" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; Antiviral Agents/*pharmacology/therapeutic use ; Cell Line ; Cell Nucleus/virology ; Cytidine/metabolism ; Cytidine Deaminase/biosynthesis ; DNA, Circular/*metabolism ; DNA, Viral/*metabolism ; Hepatitis B/*drug therapy ; Hepatitis B virus/*drug effects/metabolism ; Hepatocytes/*drug effects/metabolism/virology ; Humans ; Interferon-alpha/*pharmacology/therapeutic use ; Liver/drug effects/metabolism/virology ; Lymphotoxin beta Receptor/*agonists/antagonists & inhibitors ; Mice, SCID ; Proteins ; Up-Regulation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-06-14
    Description: Chisari et al. challenge our central conclusion that the hepatitis B virus (HBV) persistent form, the covalently closed circular DNA (cccDNA), is degraded in a noncytotoxic and specific fashion in the nucleus of infected hepatocytes. Specificity of the assays used, exclusion of cell division or death, and activity of APOBEC3 deaminases in the nucleus, however, were addressed in the paper.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xia, Yuchen -- Lucifora, Julie -- Reisinger, Florian -- Heikenwalder, Mathias -- Protzer, Ulrike -- New York, N.Y. -- Science. 2014 Jun 13;344(6189):1237. doi: 10.1126/science.1254083.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Virology, Technische Universitat Munchen, Helmholtz Zentrum Munchen, Munich, Germany. ; Institute of Virology, Technische Universitat Munchen, Helmholtz Zentrum Munchen, Munich, Germany. protzer@tum.de protzer@helmholtz-muenchen.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24926011" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiviral Agents/*pharmacology ; DNA, Circular/*metabolism ; DNA, Viral/*metabolism ; Hepatitis B/*drug therapy ; Hepatitis B virus/*drug effects ; Hepatocytes/*drug effects ; Humans ; Interferon-alpha/*pharmacology ; Lymphotoxin beta Receptor/*agonists
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
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