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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA.
Science 343, 1221-1228 (2014)
Current antivirals can control but not eliminate hepatitis-B-virus (HBV), because HBV establishes a stable nuclear cccDNA. Interferon-α treatment can clear HBV but is limited by systemic side effects. Here, we describe how interferon-α can induce specific degradation of the nuclear viral DNA without hepatotoxicity and propose lymphotoxin-β-receptor activation as a therapeutic alternative. Interferon-α and lymphotoxin-β-receptor activation up-regulated APOBEC3A and 3B 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 - e.g., by lymphotoxin-β-receptor activation - allows development of new therapeutics that combined with existing antivirals may cure hepatitis B.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Lymphotoxin-beta-receptor; Gene-expression; Hepatocellular-carcinoma; Cytidine Deaminases; Human Hepatocytes; Transgenic Mice; Hbv Infection; Foreign Dna; In-vitro; Replication
ISSN (print) / ISBN
0036-8075
e-ISSN
1095-9203
Zeitschrift
Science
Quellenangaben
Band: 343,
Heft: 6176,
Seiten: 1221-1228
Verlag
American Association for the Advancement of Science (AAAS)
Verlagsort
Washington
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Virology (VIRO)