In Vivo Bioluminescence Imaging of HBV Replicating Hepatocytes Allows for the Monitoring of Anti-Viral Immunity

Immunity against hepatitis B virus (HBV) infection is complex and not entirely understood so far, including the decisive factors leading to the development of chronic hepatitis B. This lack of a mechanistic understanding of HBV-specific immunity is also caused by a limited number of suitable animal...

Full description

Saved in:
Bibliographic Details
Published in:Viruses 2021-11, Vol.13 (11), p.2273
Main Authors: Manske, Katrin, Schneider, Annika, Ko, Chunkyu, Knolle, Percy A, Steiger, Katja, Protzer, Ulrike, Wohlleber, Dirk
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviruses
Animal models
Animals
Antiviral agents
Bioluminescence
bioluminescence imaging (BLI)
CD8 antigen
CD8 T cells
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Chronic illnesses
Chronic infection
Cloning
Cytotoxicity
Genomes
Genotype & phenotype
HBV
Hepatitis B
Hepatitis B virus - genetics
Hepatitis B virus - immunology
Hepatitis B, Chronic - genetics
Hepatitis B, Chronic - immunology
Hepatitis B, Chronic - virology
Hepatocytes
Hepatocytes - immunology
Immunity
Infections
KLRG1 protein
Laboratory animals
Liver
Liver - immunology
Liver - metabolism
Liver - pathology
Liver - virology
Lymphocytes
Lymphocytes T
Male
Mice
Mice, Inbred C57BL
PD-1 protein
T cell dysfunction
Transgenic animals
Veins & arteries
Viral infections
Virus Replication - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Immunity against hepatitis B virus (HBV) infection is complex and not entirely understood so far, including the decisive factors leading to the development of chronic hepatitis B. This lack of a mechanistic understanding of HBV-specific immunity is also caused by a limited number of suitable animal models. Here, we describe the generation of a recombinant adenovirus expressing an HBV 1.3-overlength genome linked to luciferase (Ad-HBV-Luc) allowing for precise analysis of the quantity of infected hepatocytes. This enables sensitive and close-meshed monitoring of HBV-specific CD8 T cells and the onset of anti-viral immunity in mice. A high dose of Ad-HBV-Luc developed into chronic hepatitis B accompanied by dysfunctional CD8 T cells characterized by high expression of PD1 and TOX and low expression of KLRG1 and GzmB. In contrast, a low dose of Ad-HBV-Luc infection resulted in acute hepatitis with CD8 T cell-mediated elimination of HBV-replicating hepatocytes associated with elevated sALT levels and increased numbers of cytotoxic HBV-specific CD8 T cells. Thus, the infectious dose was a critical factor to induce either acute self-limited or chronic HBV infection in mice. Taken together, the new Ad-HBV-Luc vector will allow for highly sensitive and time-resolved analysis of HBV-specific immune responses during acute and chronic infection.
ISSN:1999-4915
1999-4915
DOI:10.3390/v13112273