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Different antiviral effects of IFNα subtypes in a mouse model of HBV infection

Interferon alpha (IFNα) is commonly used for the treatment of chronic hepatitis B (CHB) patients. There are 13 different IFNα subtypes in humans, but only the subtype IFNα2 is used for clinical treatment. The antiviral activities of all other IFNα subtypes against HBV have not been studied. To obtai...

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Autores principales: Song, Jingjiao, Li, Sheng, Zhou, Yun, Liu, Jia, Francois, Sandra, Lu, Mengji, Yang, Dongliang, Dittmer, Ulf, Sutter, Kathrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428457/
https://www.ncbi.nlm.nih.gov/pubmed/28336921
http://dx.doi.org/10.1038/s41598-017-00469-1
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author Song, Jingjiao
Li, Sheng
Zhou, Yun
Liu, Jia
Francois, Sandra
Lu, Mengji
Yang, Dongliang
Dittmer, Ulf
Sutter, Kathrin
author_facet Song, Jingjiao
Li, Sheng
Zhou, Yun
Liu, Jia
Francois, Sandra
Lu, Mengji
Yang, Dongliang
Dittmer, Ulf
Sutter, Kathrin
author_sort Song, Jingjiao
collection PubMed
description Interferon alpha (IFNα) is commonly used for the treatment of chronic hepatitis B (CHB) patients. There are 13 different IFNα subtypes in humans, but only the subtype IFNα2 is used for clinical treatment. The antiviral activities of all other IFNα subtypes against HBV have not been studied. To obtain basic knowledge about the direct antiviral as well as the immunomodulatory effects of IFNα subtypes, we used the HBV hydrodynamic injection (HI) mouse model. Application of most IFNα subtype proteins inhibited HBV replication in vivo, with IFNα4 and IFNα5 being the most effective subtypes. Decreased viral loads after therapeutic application of IFNα4 and IFNα5 correlated with expanded effector cell populations of NK cells and T cells in both liver and spleen. Hydrodynamic injection of plasmids encoding for the effective IFNα subtypes (pIFNα) was even more potent against HBV than injecting IFNα proteins. The combination of pIFNα4 and pIFNα5 showed a synergistic antiviral effect on HBV replication, with a strong increase in NK cell and T cell activity. The results demonstrate distinct anti-HBV effects of different IFNα subtypes against HBV in the mouse model, which may be relevant for new therapeutic approaches.
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spelling pubmed-54284572017-05-15 Different antiviral effects of IFNα subtypes in a mouse model of HBV infection Song, Jingjiao Li, Sheng Zhou, Yun Liu, Jia Francois, Sandra Lu, Mengji Yang, Dongliang Dittmer, Ulf Sutter, Kathrin Sci Rep Article Interferon alpha (IFNα) is commonly used for the treatment of chronic hepatitis B (CHB) patients. There are 13 different IFNα subtypes in humans, but only the subtype IFNα2 is used for clinical treatment. The antiviral activities of all other IFNα subtypes against HBV have not been studied. To obtain basic knowledge about the direct antiviral as well as the immunomodulatory effects of IFNα subtypes, we used the HBV hydrodynamic injection (HI) mouse model. Application of most IFNα subtype proteins inhibited HBV replication in vivo, with IFNα4 and IFNα5 being the most effective subtypes. Decreased viral loads after therapeutic application of IFNα4 and IFNα5 correlated with expanded effector cell populations of NK cells and T cells in both liver and spleen. Hydrodynamic injection of plasmids encoding for the effective IFNα subtypes (pIFNα) was even more potent against HBV than injecting IFNα proteins. The combination of pIFNα4 and pIFNα5 showed a synergistic antiviral effect on HBV replication, with a strong increase in NK cell and T cell activity. The results demonstrate distinct anti-HBV effects of different IFNα subtypes against HBV in the mouse model, which may be relevant for new therapeutic approaches. Nature Publishing Group UK 2017-03-23 /pmc/articles/PMC5428457/ /pubmed/28336921 http://dx.doi.org/10.1038/s41598-017-00469-1 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Song, Jingjiao
Li, Sheng
Zhou, Yun
Liu, Jia
Francois, Sandra
Lu, Mengji
Yang, Dongliang
Dittmer, Ulf
Sutter, Kathrin
Different antiviral effects of IFNα subtypes in a mouse model of HBV infection
title Different antiviral effects of IFNα subtypes in a mouse model of HBV infection
title_full Different antiviral effects of IFNα subtypes in a mouse model of HBV infection
title_fullStr Different antiviral effects of IFNα subtypes in a mouse model of HBV infection
title_full_unstemmed Different antiviral effects of IFNα subtypes in a mouse model of HBV infection
title_short Different antiviral effects of IFNα subtypes in a mouse model of HBV infection
title_sort different antiviral effects of ifnα subtypes in a mouse model of hbv infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428457/
https://www.ncbi.nlm.nih.gov/pubmed/28336921
http://dx.doi.org/10.1038/s41598-017-00469-1
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