Single Hepatocyte Hepatitis B Virus Transcriptional Landscape in HIV Coinfection

Ashwin Balagopal, Hyon S. Hwang, Tanner Grudda, Jeffrey Quinn, Richard K. Sterling, Mark S. Sulkowski, Chloe L. Thio

Research output: Contribution to journalArticle

Abstract

Background: Hepatitis B virus (HBV) is a leading cause of liver failure and hepatocellular carcinoma. Approximately 10% of people with HIV also have HBV and are at higher risk of liver disease progression than in HBV monoinfection. Antivirals, common to HIV and HBV, suppress HBV DNA levels but do not eradicate virus because the transcriptional template, covalently closed circular DNA (cccDNA), is long lived in infected hepatocytes. Methods: Using single-cell laser capture microdissection, we isolated >1100 hepatocytes from 5 HIV/HBV coinfected persons with increasing exposure to HBV antivirals (HB1-HB5; no exposure to >7 years exposure), quantifying cccDNA and pregenomic RNA (pgRNA) in each cell using droplet digital polymerase chain reaction. Results: The proportion of infected hepatocytes decreased with antiviral exposure from 96.4% (HB1) to 29.8% (HB5). Upper cccDNA range and median pgRNA decreased from HB1 to HB5 (P <. 05 for both). The amount of pgRNA transcribed per cccDNA also decreased from HB1 to HB5 (P <. 05). Cells with inactive pgRNA transcription were enriched from 0% (HB1) to 14.3% (HB5) of infected hepatocytes. Conclusions: cccDNA transcription is reduced in HIV/HBV coinfected people with longer antiviral duration. Understanding HBV transcriptional regulation may be critical to develop a functional cure.

Original languageEnglish (US)
Pages (from-to)1462-1469
Number of pages8
JournalJournal of Infectious Diseases
Volume221
Issue number9
DOIs
StatePublished - Apr 7 2020

Keywords

  • HBV transcription
  • HIV/HBV coinfection
  • Intrahepatic hepatitis B
  • Single-cell laser capture microdissection
  • Viral landscape
  • Viroscape

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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