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...

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Autores principales:	Katrin Manske, Annika Schneider, Chunkyu Ko, Percy A. Knolle, Katja Steiger, Ulrike Protzer, Dirk Wohlleber
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	liver immunology immunity CD8 T cells T cell dysfunction bioluminescence imaging (BLI) HBV Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4f515b1db01a4d0f9470d29af1867d8b
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spelling	oai:doaj.org-article:4f515b1db01a4d0f9470d29af1867d8b2021-11-25T19:14:00ZIn Vivo Bioluminescence Imaging of HBV Replicating Hepatocytes Allows for the Monitoring of Anti-Viral Immunity10.3390/v131122731999-4915https://doaj.org/article/4f515b1db01a4d0f9470d29af1867d8b2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2273https://doaj.org/toc/1999-4915Immunity 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.Katrin ManskeAnnika SchneiderChunkyu KoPercy A. KnolleKatja SteigerUlrike ProtzerDirk WohlleberMDPI AGarticleliver immunologyimmunityCD8 T cellsT cell dysfunctionbioluminescence imaging (BLI)HBVMicrobiologyQR1-502ENViruses, Vol 13, Iss 2273, p 2273 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	liver immunology immunity CD8 T cells T cell dysfunction bioluminescence imaging (BLI) HBV Microbiology QR1-502
spellingShingle	liver immunology immunity CD8 T cells T cell dysfunction bioluminescence imaging (BLI) HBV Microbiology QR1-502 Katrin Manske Annika Schneider Chunkyu Ko Percy A. Knolle Katja Steiger Ulrike Protzer Dirk Wohlleber In Vivo Bioluminescence Imaging of HBV Replicating Hepatocytes Allows for the Monitoring of Anti-Viral Immunity
description	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.
format	article
author	Katrin Manske Annika Schneider Chunkyu Ko Percy A. Knolle Katja Steiger Ulrike Protzer Dirk Wohlleber
author_facet	Katrin Manske Annika Schneider Chunkyu Ko Percy A. Knolle Katja Steiger Ulrike Protzer Dirk Wohlleber
author_sort	Katrin Manske
title	In Vivo Bioluminescence Imaging of HBV Replicating Hepatocytes Allows for the Monitoring of Anti-Viral Immunity
title_short	In Vivo Bioluminescence Imaging of HBV Replicating Hepatocytes Allows for the Monitoring of Anti-Viral Immunity
title_full	In Vivo Bioluminescence Imaging of HBV Replicating Hepatocytes Allows for the Monitoring of Anti-Viral Immunity
title_fullStr	In Vivo Bioluminescence Imaging of HBV Replicating Hepatocytes Allows for the Monitoring of Anti-Viral Immunity
title_full_unstemmed	In Vivo Bioluminescence Imaging of HBV Replicating Hepatocytes Allows for the Monitoring of Anti-Viral Immunity
title_sort	in vivo bioluminescence imaging of hbv replicating hepatocytes allows for the monitoring of anti-viral immunity
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4f515b1db01a4d0f9470d29af1867d8b
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In Vivo Bioluminescence Imaging of HBV Replicating Hepatocytes Allows for the Monitoring of Anti-Viral Immunity

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