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83: Antiviral and immunomodulatory activity of different human interferon-α subtypes during chronic viral infections.

Authors :
Francois, Sandra
Berendes, Christopher
Trilling, Mirko
Piehler, Jacob
Dittmer, Ulf
Source :
Cytokine. Sep2013, Vol. 63 Issue 3, p262-263. 2p.
Publication Year :
2013

Abstract

Type I Interferons (IFNs) are a multigene family with up to 14 different IFN-α subtypes. IFNs have direct antiviral activity mediated by the induction of antiviral enzymes and they can also stimulate cells of the innate and adaptive immune system. Various studies demonstrated distinct antiviral activities of specific IFN-α subtypes, but their immunomodulatory properties during viral infections have not been investigated in detail. The immune response mediated by natural killer (NK) cells or T cells is critical for the rapid containment of virus replication and spread during acute infection. This study deals with the antiviral activity of all human IFN-α subtypes against many different viruses in vitro, their transcriptional activity and their immunomodulatory effects on NK cells and T cells in HCV-infected patients. We synthesized all human IFN-α subtypes and tested their antiviral properties against VSV, HIV-1, Influenza, HCV, HBV, EMCV and HSV-1 in vitro. We stimulated PBMCs from HCV-infected patients and healthy individuals and analyzed the modulation of immune cells by the different IFN-α subtypes. Differences in the antiviral activity of the distinct IFN-α subtypes against the tested viruses were detected. IFN-α21 was very effective in inhibiting VSV and EMCV in vitro, whereas the highest antiviral activity against HSV-1 was mediated by IFN-α8 and IFN-α4. Human IFN-α16 and IFN-α8 were the most potent inhibitors of HCV replication in vitro. Using a transgenic luciferase reporter cell line we observed that human IFN-α2, IFN-α8, IFN-α16 and IFN-α21 showed the highest transcriptional activity under the control of the ISRE promotor. Stimulation of human PBMCs with the tested IFN-α subtypes revealed differences in the modulation of effector functions of T and NK cells. These results demonstrate a unique function of each IFN-α subtype in their direct inhibition of viral infections and their modulation of the innate and adaptive immune response. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10434666
Volume :
63
Issue :
3
Database :
Academic Search Index
Journal :
Cytokine
Publication Type :
Academic Journal
Accession number :
89825524
Full Text :
https://doi.org/10.1016/j.cyto.2013.06.086