Hepatitis Delta Virus Acts as an Immunogenic Adjuvant in Hepatitis B Virus-Infected Hepatocytes

Cell Reports Medicine
Christine Y L ThamAntonio Bertoletti

Abstract

Hepatitis delta virus (HDV) requires hepatitis B virus (HBV) to complete its infection cycle and causes severe hepatitis, with limited therapeutic options. To determine the prospect of T cell therapy in HBV/HDV co-infection, we study the impact of HDV on viral antigen processing and presentation. Using in vitro models of HBV/HDV co-infection, we demonstrate that HDV boosts HBV epitope presentation, both in HBV/HDV co-infected and neighboring mono-HBV-infected cells through the upregulation of the antigen processing pathway mediated by IFN-β/λ. Liver biopsies of HBV/HDV patients confirm this upregulation. We then validate in vitro and in a HBV/HDV preclinical mouse model that HDV infection increases the anti-HBV efficacy of T cells with engineered T cell receptors. Thus, by unveiling the effect of HDV on HBV antigen presentation, we provide a framework to better understand HBV/HDV immune pathology, and advocate the utilization of engineered HBV-specific T cells as a potential treatment for HBV/HDV co-infection.

References

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Citations

Apr 4, 2021·Viruses·Katja Giersch, Maura Dandri
Jul 27, 2021·JHEP Reports : Innovation in Hepatology·Matin KohsarJulian Schulze Zur Wiesch

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Methods Mentioned

BETA
Infection
RNA assay
flow cytometry
biopsy
biopsies
ELISA
PCR
transfection
in vitro transcription
fluorescence microscopy

Software Mentioned

IDEAS
ImageStream
Kaluza )
Gene Ontology
Kaluza
Graphpad Prism

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