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Int. J. Mol. Sci. 2018, 19(9), 2771; https://doi.org/10.3390/ijms19092771

Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus

1,2,†
,
1,2,†
,
3,* and 1,2,*
1
Department of Pharmacy, College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea
2
Duksung Innovative Drug Center, Duksung Women’s University, Seoul 132-714, Korea
3
College of Pharmacy, Research Institute of Pharmaceutical Sciences and Institute for Microorganisms, Kyungpook National University, Daegu 702-701, Korea
These authors contributed equally to this study and share first authorship.
*
Authors to whom correspondence should be addressed.
Received: 20 July 2018 / Revised: 13 September 2018 / Accepted: 13 September 2018 / Published: 14 September 2018
(This article belongs to the Special Issue Hepatitis Virus Infection and Molecular Research 2018)
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Abstract

HCV genotype 2a strain JFH-1 replicates and produces viral particles efficiently in human hepatocellular carcinoma (huh) 7.5 cells, which provide a stable in vitro cell infection system for the hepatitis C virus (HCVcc system). Natural killer (NK) cells are large lymphoid cells that recognize and kill virus-infected cells. In this study, we investigated the interaction between NK cells and the HCVcc system. IL-10 is a typical immune regulatory cytokine that is produced mostly by NK cells and macrophages. IL-21 is one of the main cytokines that stimulate the activation of NK cells. First, we used anti-IL-10 to neutralize IL-10 in a coculture of NK cells and HCVcc. Anti-IL-10 treatment increased the maturation of NK cells by enhancing the frequency of the CD56+dim population in NK-92 cells. However, with anti-IL-10 treatment of NK cells in coculture with J6/JFH-1-huh 7.5 cells, there was a significant decrease in the expression of STAT1 and STAT5 proteins in NK-92 cells and an increase in the HCV Core and NS3 proteins. In addition, rIL-21 treatment increased the frequency of the CD56+dim population in NK-92 cells, Also, there was a dramatic increase in the expression of STAT1 and STAT5 proteins in rIL-21 pre-stimulated NK cells and a decrease in the expression of HCV Core protein in coculture with J6/JFH-1-huh 7.5 cells. In summary, we found that the functional activation of NK cells can be modulated by anti-IL-10 or rIL-21, which controls the expression of HCV proteins as well as HCV RNA replication. View Full-Text
Keywords: HCV; huh 7.5; natural killer cells HCV; huh 7.5; natural killer cells
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Cho, Y.J.; Lee, H.H.; Kang, H.; Cho, H. Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus. Int. J. Mol. Sci. 2018, 19, 2771.

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