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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
11:14

Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection

Published on: November 7, 2018

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Inflammatory Gene Expression Associates with Hepatitis B Virus cccDNA- but Not Integrant-Derived Transcripts in HBeAg

Andrea Magri1, James M Harris1, Valentina D'Arienzo1

  • 1Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.

Viruses
|May 28, 2022
PubMed

Insights

Chronic hepatitis B (CHB) involves interplay between the hepatitis B virus (HBV) and host immunity. This study reveals distinct transcript origins and identifies an immune gene signature linked to HBV covalently closed circular DNA (cccDNA) transcription and viral persistence.

Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Chronic hepatitis B (CHB) is a global health issue with diverse liver disease presentations.
  • Hepatitis B virus (HBV) genomes exist as episomal covalently closed circular DNA (cccDNA) or chromosomal integrants.
  • The contribution of these distinct HBV DNA forms to viral gene expression in CHB is not fully understood.

Purpose of the Study:

  • To develop and apply a quantitative PCR (qPCR) method for estimating HBV cccDNA- and integrant-derived viral transcripts.
  • To investigate the relationship between viral transcript origins, patient age, and inflammatory status in CHB.
  • To identify host immune genes associated with cccDNA transcriptional activity.

Main Methods:

  • Development of a novel qPCR assay to quantify transcripts originating from HBV cccDNA and integrated HBV DNA.
  • Application of the assay to a cohort of HBe antigen-negative CHB patients.
  • Analysis of the hepatic transcriptome to identify host genes correlated with cccDNA transcription.

Main Results:

  • Variable patterns of HBV transcripts were observed, with preS1/S2 mRNAs predominating.
  • Integrant-derived mRNA expression correlated with increasing patient age, but not inflammatory status.
  • cccDNA-derived transcripts were associated with markers of liver inflammation, and 24 immune genes were significantly linked to cccDNA transcriptional activity.

Conclusions:

  • This study differentiates transcript origins in CHB, highlighting distinct associations with host factors.
  • An immune gene signature associated with HBV cccDNA transcription provides insights into viral persistence mechanisms.
  • Understanding these viral-host interactions is crucial for managing CHB and developing therapeutic strategies.

Keywords:
cccDNAhepatitis B virusinflammationtranscription

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