Natural killer cells inhibit hepatitis C virus expression

Abstract: Natural killer (NK) cells are critical in host innate defense against certain viruses. The role of NK cells in controlling hepatitis C virus (HCV) remains obscure. We examined whether NK cells are capable of inhibiting HCV expression in human he-patic cells. When NK cells are cultured with the HCV replicon-containing hepatic cells, they have no direct cytolytic effect but release soluble factor(s) suppress-ing HCV RNA expression. Media conditioned by NK cell lines (NK-92 and YTS) or primary NK cells iso-lated from healthy donors contain interferon (IFN-) and potently inhibit HCV RNA expression. Ligation of CD81 on NK cells inhibits IFN- produc-tion and results in decreased anti-HCV activity. In addition, the antibodies to IFN- or IFN- receptors abolish the anti-HCV activity of NK cell-conditioned media. The role of IFN- in NK cell-mediated, anti-HCV activity is supported by the observation that NK cell-conditioned media enhanced expression of signal transducer and activator of transcription-1, a nu-clear factor that is essential in IFN--mediated anti-viral pathways. NK cell-conditioned media have the ability to stimulate intracellular IFN- expression in the hepatic cells, suggesting a mechanism responsible for NK cell-mediated, anti-HCV activity. Thus, NK cells hold the potential to play a vital role in control-ling HCV replication in hepatic cells using an IFN-