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.
Highlights
Hirotaka Imai1, Youki Ueda1, Shinya Satoh1, Takaji Wakita2 and Keywords HCV RNA replication; hepatitis C virus; innate immune response; Natural killer (NK) cell; ULBP1
We examined the intracellular expression of endogenous ULBP1 in PH5CH8 C-non-structural protein 2 (NS2)&NS3-5B (O) cells by flow cytometric analysis
The results showed that, in addition to the stable, exogenous expression of ULBP1 in PH5CH8 cells, the intracellular level of ULBP1 was significantly enhanced in PH5CH8 C-NS2&NS3-5B (O) cells compared with PH5CH8 Cont cells (Fig. 1D)
Summary
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. NK cell line NK-92 induced cytotoxicity and interferon-c 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. Abbreviations ADR, adriamycin; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HCMV, human cytomegalovirus; HCV, hepatitis C virus; IFN, interferon; MICA, MHC class I chain-related A; MICB, MHC class I chain-related B; NKG2A, NK group 2 member A; NKG2D, NK group 2 member D; NK, natural killer; NS2, non-structural protein 2; RAET1G, retinoic acid early transcript 1G; sMICA, soluble forms of MICA; sMICB, soluble forms of MICB; sULBP2, soluble forms of ULBP2; ULBP, UL16-binding protein; UV-JFH-1, ultraviolet-inactivated JFH-1
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