Single hepatocyte hepatitis B virus transcriptional landscape in HIV coinfection
A Balagopal, HS Hwang, T Grudda… - The Journal of …, 2020 - academic.oup.com
The Journal of Infectious Diseases, 2020•academic.oup.com
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 …
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 …
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.
Oxford University Press