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

Abstract 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....

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Main Authors: Jingjiao Song, Sheng Li, Yun Zhou, Jia Liu, Sandra Francois, Mengji Lu, Dongliang Yang, Ulf Dittmer, Kathrin Sutter
Format: Article
Language:English
Published: Nature Portfolio 2017-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-00469-1
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author Jingjiao Song
Sheng Li
Yun Zhou
Jia Liu
Sandra Francois
Mengji Lu
Dongliang Yang
Ulf Dittmer
Kathrin Sutter
author_facet Jingjiao Song
Sheng Li
Yun Zhou
Jia Liu
Sandra Francois
Mengji Lu
Dongliang Yang
Ulf Dittmer
Kathrin Sutter
author_sort Jingjiao Song
collection DOAJ
description Abstract 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 doaj.art-23174242175f492487c0baadadc7baf52022-12-21T22:56:09ZengNature PortfolioScientific Reports2045-23222017-03-017111310.1038/s41598-017-00469-1Different antiviral effects of IFNα subtypes in a mouse model of HBV infectionJingjiao Song0Sheng Li1Yun Zhou2Jia Liu3Sandra Francois4Mengji Lu5Dongliang Yang6Ulf Dittmer7Kathrin Sutter8Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Virology, University Hospital of Essen, University of Duisburg-EssenInstitute of Virology, University Hospital of Essen, University of Duisburg-EssenDepartment of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Virology, University Hospital of Essen, University of Duisburg-EssenInstitute of Virology, University Hospital of Essen, University of Duisburg-EssenAbstract 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.https://doi.org/10.1038/s41598-017-00469-1
spellingShingle Jingjiao Song
Sheng Li
Yun Zhou
Jia Liu
Sandra Francois
Mengji Lu
Dongliang Yang
Ulf Dittmer
Kathrin Sutter
Different antiviral effects of IFNα subtypes in a mouse model of HBV infection
Scientific Reports
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
url https://doi.org/10.1038/s41598-017-00469-1
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