Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice

Abstract Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled in...

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Autores principales:	Martijn D. B. van de Garde, Suzan D. Pas, Gertine W. van Oord, Lucio Gama, Youkyung Choi, Robert A. de Man, Andre Boonstra, Thomas Vanwolleghem
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/92e4c668c29940759340cefbb3ea2515
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spelling	oai:doaj.org-article:92e4c668c29940759340cefbb3ea25152021-12-02T16:07:58ZInterferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice10.1038/s41598-017-07434-y2045-2322https://doaj.org/article/92e4c668c29940759340cefbb3ea25152017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07434-yhttps://doaj.org/toc/2045-2322Abstract Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFNα doses in all mice and relapsed after a single pegIFNα injection in only half of treated animals. Rapid viral clearance by pegIFNα was confirmed in HEV gt1, but not in Hepatitis B Virus infected animals. No ISG induction was observed in untreated HEV gt3 and gt1 infected humanized livers compared to control chimeric mice, irrespective of the human hepatocyte donor, viral isolate or HEV infection duration. Human specific ISG transcript levels in mouse liver increased significantly after pegIFNα treatment and induced high circulating human CXCL10 in mouse serum. In conclusion, HEV gt1 and gt3 infections do not elicit innate intrahepatic immune responses and remain highly sensitive to pegIFNα in immunocompromised humanized mice.Martijn D. B. van de GardeSuzan D. PasGertine W. van OordLucio GamaYoukyung ChoiRobert A. de ManAndre BoonstraThomas VanwolleghemNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martijn D. B. van de Garde Suzan D. Pas Gertine W. van Oord Lucio Gama Youkyung Choi Robert A. de Man Andre Boonstra Thomas Vanwolleghem Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice
description	Abstract Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFNα doses in all mice and relapsed after a single pegIFNα injection in only half of treated animals. Rapid viral clearance by pegIFNα was confirmed in HEV gt1, but not in Hepatitis B Virus infected animals. No ISG induction was observed in untreated HEV gt3 and gt1 infected humanized livers compared to control chimeric mice, irrespective of the human hepatocyte donor, viral isolate or HEV infection duration. Human specific ISG transcript levels in mouse liver increased significantly after pegIFNα treatment and induced high circulating human CXCL10 in mouse serum. In conclusion, HEV gt1 and gt3 infections do not elicit innate intrahepatic immune responses and remain highly sensitive to pegIFNα in immunocompromised humanized mice.
format	article
author	Martijn D. B. van de Garde Suzan D. Pas Gertine W. van Oord Lucio Gama Youkyung Choi Robert A. de Man Andre Boonstra Thomas Vanwolleghem
author_facet	Martijn D. B. van de Garde Suzan D. Pas Gertine W. van Oord Lucio Gama Youkyung Choi Robert A. de Man Andre Boonstra Thomas Vanwolleghem
author_sort	Martijn D. B. van de Garde
title	Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice
title_short	Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice
title_full	Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice
title_fullStr	Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice
title_full_unstemmed	Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice
title_sort	interferon-alpha treatment rapidly clears hepatitis e virus infection in humanized mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/92e4c668c29940759340cefbb3ea2515
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Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice

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