Specific and Nonhepatotoxic Degradation of Nuclear Hepatitis B Virus cccDNA - Centre de recherche en cancérologie de Lyon (UMR INSERM 1052 ; CNRS 5286 ; Centre Léon Bérard) Accéder directement au contenu
Article Dans Une Revue Science Année : 2014

Specific and Nonhepatotoxic Degradation of Nuclear Hepatitis B Virus cccDNA

Zuzanna Makowska
  • Fonction : Auteur
Tassilo Volz
  • Fonction : Auteur
Markus H Heim
  • Fonction : Auteur
Jeffrey L Browning
  • Fonction : Auteur
Emmanuel Dejardin

Résumé

Current antiviral agents can control but not eliminate hepatitis B virus (HBV), because HBV establishes a stable nuclear covalently closed circular DNA (cccDNA). Interferon-α treatment can clear HBV but is limited by systemic side effects. 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 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-β receptor activation—allows the development of new therapeutics that, in combination with existing antivirals, may cure hepatitis B.
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Dates et versions

hal-03315632 , version 1 (06-08-2021)

Identifiants

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Julie Lucifora, Yuchen Xia, Florian Reisinger, K. Zhang, Daniela Stadler, et al.. Specific and Nonhepatotoxic Degradation of Nuclear Hepatitis B Virus cccDNA. Science, 2014, 343 (6176), pp.1221 - 1228. ⟨10.1126/science.1243462⟩. ⟨hal-03315632⟩
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