Hepatitis-D Virus Infection Is Not Impaired by Innate Immunity but Increases Cytotoxic T-Cell Activity

Approximately 70 million humans worldwide are affected by chronic hepatitis D, which rapidly leads to liver cirrhosis and hepatocellular carcinoma due to chronic inflammation. The triggers and consequences of this chronic inflammation, induced by co-infection with the hepatitis D virus (HDV) and the...

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Autores principales:	Sebastian Maximilian Altstetter, Oliver Quitt, Francesca Pinci, Veit Hornung, Aaron Michael Lucko, Karin Wisskirchen, Stephanie Jung, Ulrike Protzer
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hepatitis delta virus hepatitis B virus innate immunity MDA5 antiviral response T-cell dependent cytotoxicity Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f85702bf96bc4fbbb617d9e9030fd35b
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spelling	oai:doaj.org-article:f85702bf96bc4fbbb617d9e9030fd35b2021-11-25T17:13:19ZHepatitis-D Virus Infection Is Not Impaired by Innate Immunity but Increases Cytotoxic T-Cell Activity10.3390/cells101132532073-4409https://doaj.org/article/f85702bf96bc4fbbb617d9e9030fd35b2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3253https://doaj.org/toc/2073-4409Approximately 70 million humans worldwide are affected by chronic hepatitis D, which rapidly leads to liver cirrhosis and hepatocellular carcinoma due to chronic inflammation. The triggers and consequences of this chronic inflammation, induced by co-infection with the hepatitis D virus (HDV) and the hepatitis B virus (HBV), are poorly understood. Using CRISPR technology, we characterized the recognition of HDV mono- and co-infection by intracellular innate immunity and determined its influence on the viral life cycle and effector T-cell responses using different HBV and HDV permissive hepatoma cell lines. We showed that HDV infection is detected by MDA5 and -after a lag phase -induces a profound type I interferon response in the infected cells. The type I interferon response, however, was not able to suppress HDV replication or spread, thus providing a persistent trigger. Using engineered T-cells directed against the envelope proteins commonly used by HBV and HDV, we found that HDV immune recognition enhanced T-cell cytotoxicity. Interestingly, the T-cell effector function was enhanced independently of antigen presentation. These findings help to explain immune mediated tissue damage in chronic hepatitis D patients and indicate that combining innate triggers with T-cell activating therapies might allow for a curative approach.Sebastian Maximilian AltstetterOliver QuittFrancesca PinciVeit HornungAaron Michael LuckoKarin WisskirchenStephanie JungUlrike ProtzerMDPI AGarticlehepatitis delta virushepatitis B virusinnate immunityMDA5antiviral responseT-cell dependent cytotoxicityBiology (General)QH301-705.5ENCells, Vol 10, Iss 3253, p 3253 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatitis delta virus hepatitis B virus innate immunity MDA5 antiviral response T-cell dependent cytotoxicity Biology (General) QH301-705.5
spellingShingle	hepatitis delta virus hepatitis B virus innate immunity MDA5 antiviral response T-cell dependent cytotoxicity Biology (General) QH301-705.5 Sebastian Maximilian Altstetter Oliver Quitt Francesca Pinci Veit Hornung Aaron Michael Lucko Karin Wisskirchen Stephanie Jung Ulrike Protzer Hepatitis-D Virus Infection Is Not Impaired by Innate Immunity but Increases Cytotoxic T-Cell Activity
description	Approximately 70 million humans worldwide are affected by chronic hepatitis D, which rapidly leads to liver cirrhosis and hepatocellular carcinoma due to chronic inflammation. The triggers and consequences of this chronic inflammation, induced by co-infection with the hepatitis D virus (HDV) and the hepatitis B virus (HBV), are poorly understood. Using CRISPR technology, we characterized the recognition of HDV mono- and co-infection by intracellular innate immunity and determined its influence on the viral life cycle and effector T-cell responses using different HBV and HDV permissive hepatoma cell lines. We showed that HDV infection is detected by MDA5 and -after a lag phase -induces a profound type I interferon response in the infected cells. The type I interferon response, however, was not able to suppress HDV replication or spread, thus providing a persistent trigger. Using engineered T-cells directed against the envelope proteins commonly used by HBV and HDV, we found that HDV immune recognition enhanced T-cell cytotoxicity. Interestingly, the T-cell effector function was enhanced independently of antigen presentation. These findings help to explain immune mediated tissue damage in chronic hepatitis D patients and indicate that combining innate triggers with T-cell activating therapies might allow for a curative approach.
format	article
author	Sebastian Maximilian Altstetter Oliver Quitt Francesca Pinci Veit Hornung Aaron Michael Lucko Karin Wisskirchen Stephanie Jung Ulrike Protzer
author_facet	Sebastian Maximilian Altstetter Oliver Quitt Francesca Pinci Veit Hornung Aaron Michael Lucko Karin Wisskirchen Stephanie Jung Ulrike Protzer
author_sort	Sebastian Maximilian Altstetter
title	Hepatitis-D Virus Infection Is Not Impaired by Innate Immunity but Increases Cytotoxic T-Cell Activity
title_short	Hepatitis-D Virus Infection Is Not Impaired by Innate Immunity but Increases Cytotoxic T-Cell Activity
title_full	Hepatitis-D Virus Infection Is Not Impaired by Innate Immunity but Increases Cytotoxic T-Cell Activity
title_fullStr	Hepatitis-D Virus Infection Is Not Impaired by Innate Immunity but Increases Cytotoxic T-Cell Activity
title_full_unstemmed	Hepatitis-D Virus Infection Is Not Impaired by Innate Immunity but Increases Cytotoxic T-Cell Activity
title_sort	hepatitis-d virus infection is not impaired by innate immunity but increases cytotoxic t-cell activity
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f85702bf96bc4fbbb617d9e9030fd35b
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Hepatitis-D Virus Infection Is Not Impaired by Innate Immunity but Increases Cytotoxic T-Cell Activity

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