NDLI: Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lucifora, Julie Zhang, Ke Durantel, David Koppensteiner, Herwig Makowska, Zuzanna Cheng, Xiaoming Liang, T. Jake Xia, Yuchen Browning, Jeffrey L. Reisinger, Florian Dandri, Maura Volz, Tassilo Thasler, Wolfgang E. Chou, Wen-min Hüser, Norbert Schindler, Michael Münk, Carsten Heim, Markus H. Heikenwalder, Mathias Sprinzl, Martin F. Stadler, Daniela Remouchamps, Caroline Protzer, Ulrike Dejardin, Emmanuel
Description	Author Affiliation: Lucifora J ( Institute of Virology, Technische Universität München-Helmholtz Zentrum München, 81675 Munich, Germany.)
Abstract	Current antiviral agents can control but not eliminate hepatitis B virus (HBV), because HBV establishes a stable nuclear covalently closed circular DNA (cccDNA). Interferon- treatment can clear HBV but is limited by systemic side effects. We describe how interferon- can induce specific degradation of the nuclear viral DNA without hepatotoxicity and propose lymphotoxin-ß receptor activation as a therapeutic alternative. Interferon- and lymphotoxin-ß 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-ß receptor activation-allows the development of new therapeutics that, in combination with existing antivirals, may cure hepatitis B.
ISSN	00368075
Issue Number	6176
Volume Number	343
e-ISSN	10959203
Journal	Science
Language	English
Publisher	American Association for the Advancement of Science (United States)
Publisher Date	2014-03-14
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Antiviral Agents Pharmacology DNA, Circular Metabolism DNA, Viral Hepatitis B Virus Drug Effects Hepatitis B Drug Therapy Hepatocytes Interferon-alpha Lymphotoxin Beta Receptor Agonists Animals Antibodies, Monoclonal Therapeutic Use Cell Line Cell Nucleus Virology Cytidine Cytidine Deaminase Biosynthesis Humans Liver Antagonists & Inhibitors Mice, SCID Minor Histocompatibility Antigens Proteins Up-Regulation Journal Article Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	History and Philosophy of Science

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