In situ analysis of intrahepatic virological events in chronic hepatitis B virus infection

The Journal of Clinical Investigation
Xiaonan ZhangZhenghong Yuan

Abstract

Persistent hepatitis B virus (HBV) infection is established by the formation of an intranuclear pool of covalently closed circular DNA (cccDNA) in the liver. Very little is known about the intrahepatic distribution of HBV cccDNA in infected patients, particularly at the single-cell level. Here, we established a highly sensitive and specific ISH assay for the detection of HBV RNA, DNA, and cccDNA. The specificity of our cccDNA probe set was confirmed by its strict intranuclear signal and by a series of Southern blot analyses. Use of our in situ assay in conjunction with IHC or immunofluorescence uncovered a surprisingly mosaic distribution of viral antigens and nucleic acids. Most strikingly, a mutually exclusive pattern was found between HBV surface antigen-positive (HBsA-positive) and HBV DNA- and cccDNA-positive cells. A longitudinal observation of patients over a 1-year period of adeforvir therapy confirmed the persistence of a nuclear reservoir of viral DNA, although cytoplasmic DNA was effectively depleted in these individuals. In conclusion, our method for detecting viral nucleic acids, including cccDNA, with single-cell resolution provides a means for monitoring intrahepatic virological events in chronic HBV infection. M...Continue Reading

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Citations

Feb 24, 2016·The Journal of Clinical Investigation·Peter A Revill, Stephen A Locarnini
Jun 2, 2016·Hepatology International·Geoffrey DusheikoIvana Carey
Jan 6, 2017·Nature Reviews. Gastroenterology & Hepatology·Mala K Maini, Antonio Bertoletti
Jan 26, 2017·Médecine sciences : M/S·Maëlle Locatelli, Barbara Testoni
Apr 20, 2018·Viruses·Robert WitteUrs F Greber
Apr 11, 2018·Journal of Viral Hepatitis·J WangW Zhang
Dec 7, 2018·Journal of Virology·Atefeh KhakpoorAntonio Bertoletti
Apr 27, 2019·Science·Chengang XiangHongkui Deng
Feb 1, 2019·Gut·Antonio Bertoletti, Patrick T F Kennedy
Nov 20, 2019·The Journal of Infectious Diseases·Ashwin BalagopalChloe L Thio
Apr 2, 2020·World Journal of Gastroenterology : WJG·Diana Gabriela IacobSimona Maria Ruta
Jun 8, 2017·Viruses·Xiaoling LiNingshao Xia
Jan 27, 2021·Biosensors & Bioelectronics·Jijo LukoseSajan D George
Apr 4, 2021·Journal of Clinical Medicine·Alessia VirzìJoachim Lupberger
Apr 16, 2021·Frontiers in Microbiology·Florentin PastorAnna Salvetti
Apr 15, 2019·The Lancet. Gastroenterology & Hepatology·Peter A RevillFabien Zoulim
Nov 16, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yang WangZhenghong Yuan

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Datasets Mentioned

BETA
AB675675

Methods Mentioned

BETA
biopsies
biopsy
nuclear translocation
transfection
PCR
Assay
in vitro transcription
fluorescence microscopy

Software Mentioned

Image Studio Lite
TissueFAXS
TissueQuest
Affymetrix
ViewRNA
GraphPad Prism

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