Abstract:

Abstract ObjectiveThe numbers, subsets and function of natural killer (NK) cells altered in chronic hepatitis C virus (HCV) infected patients which indicating its association with chronic HCV infection, but the exact mechanisms remain unclear. To explore the functional effect of HCV infection on NK cells in vitro and the possible mechanism behind it.Methods Human hepatoma Huh7.5 cells were transfected with genomic RNA from cell culture adapted JC1 genotype 2a HCV strain (Huh7.5-HCVcc) and co-cultured with NK cells isolated from whole peripheral blood of concentrated healthy donors. The functional effect of HCV infection on NK cells was assessed by testing cytokine-secreting and cytotoxicity before and after co-culture.Results When co-cultrued with Huh7.5-HCV of MOI 4.8, the levels of IFN-γ, TNF-α and IL-10 secreted by NK cells were inhibited. The inhibition of secreting IFN-γ was specially significant at 6(P<0.001), 9(P<0.001) and 12(P=0.001) hours co-cultured with Huh7.5-HCV. The inhibition of secreting TNF-α was specially significant 6 h(P<0.001), 9 h(P<0.001) and 12 h(P=0.001) after co-cultured with Huh7.5-HCVcc. And the significant inhibition of secreting IL-10 appeared at 6 h(P<0.001) and 9 h(P=0.006) after co-cultured with Huh7.5-HCVcc. The strongest cytokine-secreting inhibition appeared 6 h after co-cultured with Huh7.5-HCVcc, the inhibition rate was 24.1%, 20.7% and 24.3%, respectively. The cytotoxicity decreased significantly 6 h after co-cultured with Huh7.5-HCVcc(P=0.023), and the average inhibition rate was 16.6%.Conclusion When in vitro cocultrued with Huh7.5-HCVcc of MOI 4.8, the NK cells functions of IFN-γ, TNF-α and IL-10 cytokine-secreting and cytotoxicity were inhibited. The degree of inhibition was different at different time points, which indicated that NK cells may act differently during HCV infection.