Intrinsic Immune Response of HBV/HDV-Infected Cells and Corresponding Innate (Like) Immune Cell Activation

Infection of hepatitis B (HBV) patients with hepatitis D (HDV) can cause the most severe form of viral hepatitis, leading to liver fibrosis, liver failure, and hepatocellular carcinoma. HDV relies on simultaneous infection with HBV for the generation of infectious viral particles. The innate immune...

Full description

Saved in:
Bibliographic Details
Main Authors: Christopher Groth, Svea Wupper, Gnimah Eva Gnouamozi, Katrin Böttcher, Adelheid Cerwenka
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Livers
Subjects:
Online Access:https://www.mdpi.com/2673-4389/4/4/40
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850050310370754560
author Christopher Groth
Svea Wupper
Gnimah Eva Gnouamozi
Katrin Böttcher
Adelheid Cerwenka
author_facet Christopher Groth
Svea Wupper
Gnimah Eva Gnouamozi
Katrin Böttcher
Adelheid Cerwenka
author_sort Christopher Groth
collection DOAJ
description Infection of hepatitis B (HBV) patients with hepatitis D (HDV) can cause the most severe form of viral hepatitis, leading to liver fibrosis, liver failure, and hepatocellular carcinoma. HDV relies on simultaneous infection with HBV for the generation of infectious viral particles. The innate immune response, which is weakly induced in HBV infection, becomes strongly activated upon HDV co-infection. In HBV/HDV co-infection, the immune system comprises a cell-intrinsic strong IFN response, which leads to the induction of interferon-stimulated genes (ISGs), the local activation of liver-resident innate immune cells, and additional immune cell recruitment from the blood. Efficient innate immune responses are indispensable for successful viral control and spontaneous viral clearance. Despite this fact, innate immune cell activation can also contribute to adaptive immune cell inhibition and accelerate liver damage in HBV/HDV infection. While the intrinsic IFN response in HDV-infected cells is well characterized, far less is known about the cellular innate immune cell compartment. In this review, we summarize HBV/HDV replication characteristics and decipher the role of innate immune cell subsets in the anti-viral response in HBV/HDV infections. We further review the impact of epigenetic and metabolic changes in infected heptatocytes on the innate anti-viral response. Moreover, we discuss the potential of exploiting the innate immune response for improving vaccination strategies and treatment options, which is also discussed in this review.
format Article
id doaj-art-fe8caab736c2403dbe8f5798677f2ad9
institution DOAJ
issn 2673-4389
language English
publishDate 2024-11-01
publisher MDPI AG
record_format Article
series Livers
spelling doaj-art-fe8caab736c2403dbe8f5798677f2ad92025-08-20T02:53:30ZengMDPI AGLivers2673-43892024-11-014456259310.3390/livers4040040Intrinsic Immune Response of HBV/HDV-Infected Cells and Corresponding Innate (Like) Immune Cell ActivationChristopher Groth0Svea Wupper1Gnimah Eva Gnouamozi2Katrin Böttcher3Adelheid Cerwenka4Department of Immunobiochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanyDepartment of Immunobiochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanyDepartment of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, 69120 Heidelberg, GermanySchool of Medicine and Health, Clinical Department for Internal Medicine II, TUM University Hospital, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, GermanyDepartment of Immunobiochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanyInfection of hepatitis B (HBV) patients with hepatitis D (HDV) can cause the most severe form of viral hepatitis, leading to liver fibrosis, liver failure, and hepatocellular carcinoma. HDV relies on simultaneous infection with HBV for the generation of infectious viral particles. The innate immune response, which is weakly induced in HBV infection, becomes strongly activated upon HDV co-infection. In HBV/HDV co-infection, the immune system comprises a cell-intrinsic strong IFN response, which leads to the induction of interferon-stimulated genes (ISGs), the local activation of liver-resident innate immune cells, and additional immune cell recruitment from the blood. Efficient innate immune responses are indispensable for successful viral control and spontaneous viral clearance. Despite this fact, innate immune cell activation can also contribute to adaptive immune cell inhibition and accelerate liver damage in HBV/HDV infection. While the intrinsic IFN response in HDV-infected cells is well characterized, far less is known about the cellular innate immune cell compartment. In this review, we summarize HBV/HDV replication characteristics and decipher the role of innate immune cell subsets in the anti-viral response in HBV/HDV infections. We further review the impact of epigenetic and metabolic changes in infected heptatocytes on the innate anti-viral response. Moreover, we discuss the potential of exploiting the innate immune response for improving vaccination strategies and treatment options, which is also discussed in this review.https://www.mdpi.com/2673-4389/4/4/40hepatitis virusHBVHDVinnate immunityNK cellsγδ T cells
spellingShingle Christopher Groth
Svea Wupper
Gnimah Eva Gnouamozi
Katrin Böttcher
Adelheid Cerwenka
Intrinsic Immune Response of HBV/HDV-Infected Cells and Corresponding Innate (Like) Immune Cell Activation
Livers
hepatitis virus
HBV
HDV
innate immunity
NK cells
γδ T cells
title Intrinsic Immune Response of HBV/HDV-Infected Cells and Corresponding Innate (Like) Immune Cell Activation
title_full Intrinsic Immune Response of HBV/HDV-Infected Cells and Corresponding Innate (Like) Immune Cell Activation
title_fullStr Intrinsic Immune Response of HBV/HDV-Infected Cells and Corresponding Innate (Like) Immune Cell Activation
title_full_unstemmed Intrinsic Immune Response of HBV/HDV-Infected Cells and Corresponding Innate (Like) Immune Cell Activation
title_short Intrinsic Immune Response of HBV/HDV-Infected Cells and Corresponding Innate (Like) Immune Cell Activation
title_sort intrinsic immune response of hbv hdv infected cells and corresponding innate like immune cell activation
topic hepatitis virus
HBV
HDV
innate immunity
NK cells
γδ T cells
url https://www.mdpi.com/2673-4389/4/4/40
work_keys_str_mv AT christophergroth intrinsicimmuneresponseofhbvhdvinfectedcellsandcorrespondinginnatelikeimmunecellactivation
AT sveawupper intrinsicimmuneresponseofhbvhdvinfectedcellsandcorrespondinginnatelikeimmunecellactivation
AT gnimahevagnouamozi intrinsicimmuneresponseofhbvhdvinfectedcellsandcorrespondinginnatelikeimmunecellactivation
AT katrinbottcher intrinsicimmuneresponseofhbvhdvinfectedcellsandcorrespondinginnatelikeimmunecellactivation
AT adelheidcerwenka intrinsicimmuneresponseofhbvhdvinfectedcellsandcorrespondinginnatelikeimmunecellactivation