Natural killer cells in hepatitis C: Current progress

Figure 1 Interactions of natural killer cells with hepatitis C virus-infected hepatocytes and accessory cells. A: HCV virions may inhibit NK cells by cross-linking of CD81 on the NK cells with the HCV E2 protein, if the HCV virions are immobilized and concentrated; B: Direct cell-to-cell contact of NK cells with HCV-infected hepatoma cells reduces functional capacity of NK cells by downregulating the activating receptors NKG2D and NKp30; C: Exosomes harboring the HCV RNA are released from HCV-infected hepatoma cells and stimulate pDCs to secrete IFN-α which activates NK cells; D: The interaction with hepatoma cells containing HCV replicons stimulates monocytes to secrete IL-18 which activates NK cells; E: The HCV NS5A protein from HCV-infected hepatoma cells stimulates monocytes to secrete IL-10 and TGF-β which suppress NK cell function. HCV: Hepatitis C virus; NK cell: Natural killer cell; pDC: Plasmacytoid dendritic cell; IFN: Interferon; IL: Interleukin; TGF: Transforming growth factor; E2: Envelope 2 protein; NS5A: Nonstructural 5A protein. NKG2D: Natural killer group 2D.