Kupke, Paul and Adenugba, Akinbami and Schemmerer, Mathias and Bitterer, Florian and Schlitt, Hans J. and Geissler, Edward K. and Wenzel, Juergen J. and Werner, Jens M. (2023) 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. CELLS, 12 (3): 453. ISSN , 2073-4409
Full text not available from this repository. (Request a copy)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-gamma 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-gamma response and thus, to an additive antiviral effect in the context of an in vitro HEV infection.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | THERAPY; REPLICATION; POLYMERASE; MUTATION; RECEPTOR; IMPROVES; TYPE-1; IL-12; ribavirin; hepatitis E virus; transplantation; immunosuppression; NK cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2024 10:18 |
| Last Modified: | 08 Mar 2024 10:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59120 |
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