Specific and Nonhepatotoxic Degradation of Nuclear Hepatitis B Virus cccDNA
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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-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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
The record
- Venue
- Science
- Topic
- Hepatitis B Virus Studies
- Field
- Medicine
- Canadian institutions
- —
- Funders
- National Institutes of HealthPartenariat Canadien Contre Le CancerDeutsche Forschungsgemeinschaft
- Keywords
- cccDNAHepatitis B virusLymphotoxinVirologyCytidine deaminaseCytidineBiologyHepatitis B virus PRE betaDNAVirusHepatitis B virus DNA polymeraseReceptorEnzymeBiochemistry
- Has abstract in OpenAlex
- yes