Immunomodulation of Natural Killer Cell Function by Ribavirin Involves TYK-2 Activation and Subsequent Increased IFN-γ Secretion in the Context of In Vitro Hepatitis E Virus Infection

URN to cite this document:

urn:nbn:de:bvb:355-epub-536752 Copy

DOI to cite this document:

10.5283/epub.53675 Copy

Kupke, Paul ; Adenugba, Akinbami ; Schemmerer, Mathias ; Bitterer, Florian ; Schlitt, Hans J. ; Geissler, Edward K. ; Wenzel, Jürgen J. ; Werner, Jens M.

License: Creative Commons Attribution 4.0 PDF - Published Version (7MB)

Date of publication of this fulltext: 06 Feb 2023 07:47

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Details

Item type:	Article
Open Access Type:	Gold (with APC)
Höhe Gebühr (aus OpenAPC):	2358.06
Institution der Zahlung:	Regensburg U
Journal or Publication Title:	Cells
Publisher:	MDPI
Volume:	12
Number of Issue or Book Chapter:	3
Page Range:	p. 453
Date:	31 January 2023
Institutions:	Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Identification Number:	Value Type 10.3390/cells12030453 DOI
Keywords:	ribavirin; hepatitis E virus; transplantation; immunosuppression; NK cells
Dewey Decimal Classification:	600 Technology > 610 Medical sciences Medicine
Status:	Published
Refereed:	Yes, this version has been refereed
Created at the University of Regensburg:	Yes
Item ID:	53675

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Abstract

Hepatitis E virus (HEV) is a major cause of acute hepatitis globally. Chronic and fulminant courses are observed especially in immunocompromised transplant recipients since administration of ribavirin (RBV) does not always lead to a sustained virologic response. By in vitro stimulation of NK cells through hepatoma cell lines inoculated with a full-length HEV and treatment with RBV, we analyzed ...

Abstract

Hepatitis E virus (HEV) is a major cause of acute hepatitis globally. Chronic and fulminant courses are observed especially in immunocompromised transplant recipients since administration of ribavirin (RBV) does not always lead to a sustained virologic response. By in vitro stimulation of NK cells through hepatoma cell lines inoculated with a full-length HEV and treatment with RBV, we analyzed the viral replication and cell response to further elucidate the mechanism of action of RBV on immune cells, especially NK cells, in the context of HEV infection. Co-culture of HEV-infected hepatoma cells with PBMCs and treatment with RBV both resulted in a decrease in viral replication, which in combination showed an additive effect. An analysis of NK cell functions after stimulation revealed evidence of reduced cytotoxicity by decreased TRAIL and CD107a degranulation. Simultaneously, IFN-ɣ production was significantly increased through the IL-12R pathway. Although there was no direct effect on the IL-12R subunits, downstream events starting with TYK-2 and subsequently pSTAT4 were upregulated. In conclusion, we showed that RBV has an immunomodulatory effect on the IL-12R pathway of NK cells via TYK-2. This subsequently leads to an enhanced IFN-ɣ response and thus, to an additive antiviral effect in the context of an in vitro HEV infection.

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Metadata last modified: 11 Jul 2023 08:20

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