ULBP1 is Induced by Hepatitis C Virus Infection and is the Target of the NK Cell-mediated Innate Immune Response in Human Hepatocytes

Overview

Journal FEBS Open Bio

Specialty Biology

Date 2018 Mar 8

PMID 29511613

Citations 5

Authors

Hiromichi Dansako

Hirotaka Imai

Youki Ueda

Shinya Satoh

Takaji Wakita

Nobuyuki Kato

Affiliations

Soon will be listed here.

Abstract

Natural killer (NK) cells through their NK group 2 member D (NKG2D) receptors recognize NKG2D ligands such as UL16-binding proteins (ULBPs) on virus-infected cells and subsequently trigger the host innate immune response. In the present study, we demonstrated that hepatitis C virus (HCV) induced the cell surface expression of ULBP1 in human immortalized hepatocyte PH5CH8 cells and human hepatoma HuH-7 cell-derived RSc cells. Interestingly, NK cell line NK-92 induced cytotoxicity and interferon-γ mRNA expression and subsequently reduced the levels of HCV RNA replication during co-culture with HCV-infected RSc cells. From these results, we conclude that ULBP1 is a target of the NK cell-mediated innate immune response in HCV-infected human hepatocytes.

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References

De Maria A, Fogli M, Mazza S, Basso M, Picciotto A, Costa P . Increased natural cytotoxicity receptor expression and relevant IL-10 production in NK cells from chronically infected viremic HCV patients. Eur J Immunol. 2007; 37(2):445-55. DOI: 10.1002/eji.200635989. View

Dansako H, Ikeda M, Kato N . Limited suppression of the interferon-beta production by hepatitis C virus serine protease in cultured human hepatocytes. FEBS J. 2007; 274(16):4161-76. DOI: 10.1111/j.1742-4658.2007.05942.x. View

Amadei B, Urbani S, Cazaly A, Fisicaro P, Zerbini A, Ahmed P . Activation of natural killer cells during acute infection with hepatitis C virus. Gastroenterology. 2010; 138(4):1536-45. PMC: 4183834. DOI: 10.1053/j.gastro.2010.01.006. View

Jinushi M, Takehara T, Tatsumi T, Kanto T, Miyagi T, Suzuki T . Negative regulation of NK cell activities by inhibitory receptor CD94/NKG2A leads to altered NK cell-induced modulation of dendritic cell functions in chronic hepatitis C virus infection. J Immunol. 2004; 173(10):6072-81. DOI: 10.4049/jimmunol.173.10.6072. View

Naka K, Dansako H, Kobayashi N, Ikeda M, Kato N . Hepatitis C virus NS5B delays cell cycle progression by inducing interferon-beta via Toll-like receptor 3 signaling pathway without replicating viral genomes. Virology. 2005; 346(2):348-62. DOI: 10.1016/j.virol.2005.10.023. View

Oliviero B, Varchetta S, Paudice E, Michelone G, Zaramella M, Mavilio D . Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections. Gastroenterology. 2009; 137(3):1151-60, 1160.e1-7. DOI: 10.1053/j.gastro.2009.05.047. View

Tatsumi T, Takehara T . Impact of natural killer cells on chronic hepatitis C and hepatocellular carcinoma. Hepatol Res. 2015; 46(5):416-22. DOI: 10.1111/hepr.12619. View

Dansako H, Hiramoto H, Ikeda M, Wakita T, Kato N . Rab18 is required for viral assembly of hepatitis C virus through trafficking of the core protein to lipid droplets. Virology. 2014; 462-463:166-74. DOI: 10.1016/j.virol.2014.05.017. View

Rehermann B . Natural Killer Cells in Viral Hepatitis. Cell Mol Gastroenterol Hepatol. 2015; 1(6):578-588. PMC: 4678927. DOI: 10.1016/j.jcmgh.2015.09.004. View

10.

Raneros A, Suarez-Alvarez B, Lopez-Larrea C . Secretory pathways generating immunosuppressive NKG2D ligands: New targets for therapeutic intervention. Oncoimmunology. 2014; 3:e28497. PMC: 4063154. DOI: 10.4161/onci.28497. View

11.

Ikeda M, Sugiyama K, Mizutani T, Tanaka T, Tanaka K, Sekihara H . Human hepatocyte clonal cell lines that support persistent replication of hepatitis C virus. Virus Res. 1998; 56(2):157-67. DOI: 10.1016/s0168-1702(98)00063-x. View

12.

Matusali G, Tchidjou H, Pontrelli G, Bernardi S, DEttorre G, Vullo V . Soluble ligands for the NKG2D receptor are released during HIV-1 infection and impair NKG2D expression and cytotoxicity of NK cells. FASEB J. 2013; 27(6):2440-50. DOI: 10.1096/fj.12-223057. View

13.

Gong J, Maki G, Klingemann H . Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia. 1994; 8(4):652-8. View

14.

Dansako H, Ueda Y, Okumura N, Satoh S, Sugiyama M, Mizokami M . The cyclic GMP-AMP synthetase-STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly. FEBS J. 2015; 283(1):144-56. DOI: 10.1111/febs.13563. View

15.

Ebihara T, Masuda H, Akazawa T, Shingai M, Kikuta H, Ariga T . Induction of NKG2D ligands on human dendritic cells by TLR ligand stimulation and RNA virus infection. Int Immunol. 2007; 19(10):1145-55. DOI: 10.1093/intimm/dxm073. View

16.

Ward J, Davis Z, DeHart J, Zimmerman E, Bosque A, Brunetta E . HIV-1 Vpr triggers natural killer cell-mediated lysis of infected cells through activation of the ATR-mediated DNA damage response. PLoS Pathog. 2009; 5(10):e1000613. PMC: 2747015. DOI: 10.1371/journal.ppat.1000613. View

17.

Machida K, Cheng K, Sung V, Lee K, Levine A, Lai M . Hepatitis C virus infection activates the immunologic (type II) isoform of nitric oxide synthase and thereby enhances DNA damage and mutations of cellular genes. J Virol. 2004; 78(16):8835-43. PMC: 479064. DOI: 10.1128/JVI.78.16.8835-8843.2004. View

18.

Rolle A, Mousavi-Jazi M, Eriksson M, Odeberg J, Soderberg-Naucler C, Cosman D . Effects of human cytomegalovirus infection on ligands for the activating NKG2D receptor of NK cells: up-regulation of UL16-binding protein (ULBP)1 and ULBP2 is counteracted by the viral UL16 protein. J Immunol. 2003; 171(2):902-8. DOI: 10.4049/jimmunol.171.2.902. View

19.

Choo Q, Kuo G, Weiner A, Overby L, Bradley D, Houghton M . Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989; 244(4902):359-62. DOI: 10.1126/science.2523562. View

20.

Hedlund M, Nagaeva O, Kargl D, Baranov V, Mincheva-Nilsson L . Thermal- and oxidative stress causes enhanced release of NKG2D ligand-bearing immunosuppressive exosomes in leukemia/lymphoma T and B cells. PLoS One. 2011; 6(2):e16899. PMC: 3045385. DOI: 10.1371/journal.pone.0016899. View