Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice

Abstract Co-infection with hepatitis B (HBV) and D virus (HDV) is associated with the most severe course of liver disease. Interferon represents the only treatment currently approved. However, knowledge about the impact of interferons on HDV in human hepatocytes is scant. Aim was to assess the effec...

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Autores principales:	Katja Giersch, Maria Homs, Tassilo Volz, Martina Helbig, Lena Allweiss, Ansgar W. Lohse, Jörg Petersen, Maria Buti, Teresa Pollicino, Camille Sureau, Maura Dandri, Marc Lütgehetmann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9e42cac1eded48feb29e6600c0ba9101
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spelling	oai:doaj.org-article:9e42cac1eded48feb29e6600c0ba91012021-12-02T16:08:12ZBoth interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice10.1038/s41598-017-03946-92045-2322https://doaj.org/article/9e42cac1eded48feb29e6600c0ba91012017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03946-9https://doaj.org/toc/2045-2322Abstract Co-infection with hepatitis B (HBV) and D virus (HDV) is associated with the most severe course of liver disease. Interferon represents the only treatment currently approved. However, knowledge about the impact of interferons on HDV in human hepatocytes is scant. Aim was to assess the effect of pegylated interferon alpha (peg-IFNα) and lambda (peg-IFNλ), compared to the HBV-polymerase inhibitor entecavir (ETV) on all HDV infection markers using human liver chimeric mice and novel HDV strand-specific qRT-PCR and RNA in situ hybridization assays, which enable intrahepatic detection of HDV RNA species. Peg-IFNα and peg-IFNλ reduced HDV viremia (1.4 log and 1.2 log, respectively) and serum HBsAg levels (0.9-log and 0.4-log, respectively). Intrahepatic quantification of genomic and antigenomic HDV RNAs revealed a median ratio of 22:1 in untreated mice, resembling levels determined in HBV/HDV infected patients. Both IFNs greatly reduced intrahepatic levels of genomic and antigenomic HDV RNA, increasing the amounts of HDAg- and antigenomic RNA-negative hepatocytes. ETV-mediated suppression of HBV replication (2.1-log) did not significantly affect HBsAg levels, HDV productivity and/or release. In humanized mice lacking adaptive immunity, IFNs but not ETV suppressed HDV. Viremia decrease reflected the intrahepatic reduction of all HDV markers, including the antigenomic template, suggesting that intracellular HDV clearance is achievable.Katja GierschMaria HomsTassilo VolzMartina HelbigLena AllweissAnsgar W. LohseJörg PetersenMaria ButiTeresa PollicinoCamille SureauMaura DandriMarc LütgehetmannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katja Giersch Maria Homs Tassilo Volz Martina Helbig Lena Allweiss Ansgar W. Lohse Jörg Petersen Maria Buti Teresa Pollicino Camille Sureau Maura Dandri Marc Lütgehetmann Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice
description	Abstract Co-infection with hepatitis B (HBV) and D virus (HDV) is associated with the most severe course of liver disease. Interferon represents the only treatment currently approved. However, knowledge about the impact of interferons on HDV in human hepatocytes is scant. Aim was to assess the effect of pegylated interferon alpha (peg-IFNα) and lambda (peg-IFNλ), compared to the HBV-polymerase inhibitor entecavir (ETV) on all HDV infection markers using human liver chimeric mice and novel HDV strand-specific qRT-PCR and RNA in situ hybridization assays, which enable intrahepatic detection of HDV RNA species. Peg-IFNα and peg-IFNλ reduced HDV viremia (1.4 log and 1.2 log, respectively) and serum HBsAg levels (0.9-log and 0.4-log, respectively). Intrahepatic quantification of genomic and antigenomic HDV RNAs revealed a median ratio of 22:1 in untreated mice, resembling levels determined in HBV/HDV infected patients. Both IFNs greatly reduced intrahepatic levels of genomic and antigenomic HDV RNA, increasing the amounts of HDAg- and antigenomic RNA-negative hepatocytes. ETV-mediated suppression of HBV replication (2.1-log) did not significantly affect HBsAg levels, HDV productivity and/or release. In humanized mice lacking adaptive immunity, IFNs but not ETV suppressed HDV. Viremia decrease reflected the intrahepatic reduction of all HDV markers, including the antigenomic template, suggesting that intracellular HDV clearance is achievable.
format	article
author	Katja Giersch Maria Homs Tassilo Volz Martina Helbig Lena Allweiss Ansgar W. Lohse Jörg Petersen Maria Buti Teresa Pollicino Camille Sureau Maura Dandri Marc Lütgehetmann
author_facet	Katja Giersch Maria Homs Tassilo Volz Martina Helbig Lena Allweiss Ansgar W. Lohse Jörg Petersen Maria Buti Teresa Pollicino Camille Sureau Maura Dandri Marc Lütgehetmann
author_sort	Katja Giersch
title	Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice
title_short	Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice
title_full	Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice
title_fullStr	Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice
title_full_unstemmed	Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice
title_sort	both interferon alpha and lambda can reduce all intrahepatic hdv infection markers in hbv/hdv infected humanized mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9e42cac1eded48feb29e6600c0ba9101
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Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice

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