Hepatitis B virus cccDNA is formed through distinct repair processes of each strand.

TitleHepatitis B virus cccDNA is formed through distinct repair processes of each strand.
Publication TypeJournal Article
Year of Publication2021
AuthorsWei, L, Ploss, A
JournalNat Commun
Volume12
Issue1
Pagination1591
Date Published2021 03 11
ISSN2041-1723
KeywordsCell Line, Tumor, DNA Ligase ATP, DNA Polymerase III, DNA Repair, DNA Replication, DNA, Circular, DNA, Viral, Flap Endonucleases, Hep G2 Cells, Hepatitis B virus, Hepatitis B, Chronic, Humans, Proliferating Cell Nuclear Antigen, Replication Protein C, Virus Replication
Abstract

<p>Hepatitis B virus (HBV) is a highly contagious pathogen that afflicts over a third of the world's population, resulting in close to a million deaths annually. The formation and persistence of the HBV covalently closed circular DNA (cccDNA) is the root cause of HBV chronicity. However, the detailed molecular mechanism of cccDNA formation from relaxed circular DNA (rcDNA) remains opaque. Here we show that the minus and plus-strand lesions of HBV rcDNA require different sets of human repair factors in biochemical repair systems. We demonstrate that the plus-strand repair resembles DNA lagging strand synthesis, and requires proliferating cell nuclear antigen (PCNA), the replication factor C (RFC) complex, DNA polymerase delta (POLδ), flap endonuclease 1 (FEN-1), and DNA ligase 1 (LIG1). Only FEN-1 and LIG1 are required for the repair of the minus strand. Our findings provide a detailed mechanistic view of how HBV rcDNA is repaired to form cccDNA in biochemical repair systems.</p>

DOI10.1038/s41467-021-21850-9
Alternate JournalNat Commun
PubMed ID33707452
PubMed Central IDPMC7952586
Grant ListR01 AI138797 / AI / NIAID NIH HHS / United States
R01 AI153236 / AI / NIAID NIH HHS / United States