Distribution of hepatitis B virus nuclear DNA

Mingming Li, Ji A. Sohn, Christoph Seeger

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Chronic hepatitis B affects over 300 million people who are at risk of developing liver cancer. The basis for the persistence of hepatitis B virus (HBV) in hepatocytes, even in the presence of available antiviral therapies, lies in the accumulation of covalently closed circular DNA (cccDNA) in nuclei of infected cells. While methods for cccDNA quantification from liver biopsy specimens and cell lines expressing the virus are known, information about cccDNA formation, stability, and turnover is lacking. In particular, little is known about the fate of cccDNA during cell division. To fill the gaps in knowledge concerning cccDNA biology, we have developed a fluorescence imaging in situ hybridization (FISH)-based assay for the detection of duck hepatitis B virus (DHBV) cccDNA and HBV nuclear DNA in established cell lines. Using FISH, we determined the distribution of cccDNA under conditions mimicking chronic infections with and without antiviral therapy, which prevents de novo viral replication. Our results showed that the copy numbers of viral nuclear DNA can vary by as much as 1.8 orders of magnitude among individual cells and that antiviral therapy leads to a reduction in nuclear DNA in a manner consistent with symmetrical distribution of viral DNA to daughter cells.

Original languageEnglish
Article numbere01391-17
JournalJournal of Virology
Volume92
Issue number1
DOIs
StatePublished - Jan 1 2018

Keywords

  • Animals
  • Antiviral Agents/pharmacology
  • Cell Division/genetics
  • DNA Replication/drug effects
  • DNA, Circular/isolation & purification
  • DNA, Viral/drug effects
  • Hepatitis B Virus, Duck/genetics
  • Hepatitis B virus/genetics
  • Hepatitis B, Chronic/drug therapy
  • Hepatocytes/virology
  • In Situ Hybridization, Fluorescence/methods
  • Virus Replication

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