Previous studies examining NK cell function from HCV-infected patients have demonstrated a decrease in the cytotoxic ability of NK cells from chronically infected patients [6, 22] and altered expression of lytic proteins such as perforin [8]. In contrast, recent work by Yoon et al. [26] using in vitro–generated HCV particles shows no effect of HCV in NK cell function. The difference between that study and the other studies may be

that the viral particles used in the latter study were not lymphotropic [26]. In our experimental setting, the expression of HCV core in YTS led to a significant decrease in cytotoxicity at 120 h after transduction, but not at Dactolisib supplier an earlier time point (24 h). This difference could be due to the kinetics of core expression in YTS cells,

as core was detected in <20% of YTS cells 24 h after transduction (data not shown). In regard to the surface receptor expression pattern, some authors show an increase in natural receptors expression [21] and others observe a decrease in the percentage of NKp46 and NKp30 expressing NK cells in chronic patients [22]. In our hands, NKp46 expression was decreased in coreGFP+ YTS NK cells. However, CP868596 as YTS NK cells do not express inhibitory receptors, we were unable to test whether HCV core protein could affect their expression, as others have observed in HCV infection [21]. In summary, we found alterations in the cytotoxic potential of NK cells and in the production of IFNγ by HCV core protein. The prolonged expression of HCV core protein in YTS NK cells Tau-protein kinase led to a significant decrease in

the cytotoxic activity of the cells, in agreement with published data [6, 8, 23]. This drop in cytotoxicity was in accordance with a reduction in the expression of cytolytic proteins such as perforin and granzyme B in unstimulated and CD16-stimulated YTS NK cells. However, interestingly, this reduction in expression could be overcome by IL-2 stimulation. The reduction in cytotoxic proteins was also detected by gene array analysis, suggesting that core protein affected the level of these proteins at the level of gene transcription. Natural killer cells are a major source of cytokines such as TNF and IFNγ that have antiviral effects and play an essential role in the modulation of the subsequent adaptive immune response against intracellular pathogens [27, 28]. CoreGFP+ YTS NK cells showed a significant decrease in IFNγ production either when stimulated with anti-CD16 Ab or IL-2. Other cytokines assayed such as TNF and IL-10, IL-13, IL-4, IL-2 and TGFβ were not significantly modified in their pattern of expression by HCV core (data not shown). In the present study, we found that HCV nucleocapsid core protein expression in YTS NK cells can affect their function. It has recently been demonstrated that influenza infection of NK cells could also alter cytotoxicity and cytokine production by NK cells.