A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond?

A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond?

Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of a pregenomic (pg) RNA, yielding an unusually structured, viral polymerase-linked relaxed-circular (RC) DNA as genome in infectious particles. Upon infection, RC-DNA is conve...

Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA.

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...

Hepatitis B Virus and DNA Damage Response: Interactions and Consequences for the Infection

Hepatitis B virus (HBV) is a major etiologic agent of acute and chronic hepatitis, and end-stage liver disease. Establishment of HBV infection, progression to persistency and pathogenesis are determined by viral and cellular factors, some of which remain still undefined. Key steps of HBV life cycle e.g., transformation of genomic viral DNA into transcriptionally active episomal DNA (cccDNA) or ...

Virology. Response to Comment on "Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA".

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.

Host immune response and variations in the virus genome: pathogenesis of liver damage caused by hepatitis B virus.