Natural cytotoxicity receptor-dependent natural killer cytolytic activity directed at hepatitis C Virus (HCV) is associated with liver inflammation, African American race, IL28B genotype, and response to pegylated interferon/ribavirin therapy in chronic H
Natural cytotoxicity receptor-dependent natural killer cytolytic activity directed at hepatitis C Virus (HCV) is associated with liver inflammation, African American race, IL28B genotype, and response to pegylated interferon/ribavirin therapy in chronic H
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针对丙型肝炎病毒 (HCV) 的天然细胞毒性受体依赖性自然杀伤细胞杀伤活性与肝脏炎症、非裔美国人种族、IL28B 基因型以及慢性丙型肝炎患者对聚乙二醇干扰素/利巴韦林治疗的反应相关。
DOI：
10.1093/infdis/jit677
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Anthony,DonaldD
中科院分区：
文献类型：
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作者：
Meng,Qinglai;Rani,MRSandhya;Sugalski,JuliaM;Judge,ChelseyJ;Phat,Sarah;Rodriguez,Benigno;Blanton,RonaldE;Anthony,DonaldD
背景：自然杀伤（NK）细胞与丙型肝炎病毒（HCV）感染的发病机制和基于干扰素（IFN）-α的治疗结果有关，尽管机制尚不清楚。我们分析了健康供体和HCV感染供体NK细胞针对HCV感染靶细胞的细胞溶解活性。结果。HCV感染受试者的天然细胞毒性受体（NCR）依赖性NK-针对HCV感染和未感染的Huh7.5靶细胞的细胞溶解活性大于来自健康供体的细胞的细胞溶解活性，并且这局限于非洲裔美国人亚群。然而，IFN-α增强的NK细胞溶解功能在HCV感染的受试者中较低，再次主要局限于非洲裔美国人亚群。此外，尽管HCV感染的Huh7.5细胞比未感染的细胞更容易被靶向，但在HCV感染期间和IFN-α刺激后，对感染靶标的细胞溶解活性的选择性较低，并且较低的选择性部分归因于较高的NKp 46表达。此外，细胞溶解活性与较高的血清天冬氨酸转氨酶、rs 12979860 IL 28 B基因型和体内对聚乙二醇化IFN/利巴韦林治疗的反应有关。
Background.Natural killer (NK) cells are implicated in the pathogenesis of hepatitis C virus (HCV) infection and outcome of interferon (IFN)-α based therapy, although mechanisms remain unclear.Methods.To evaluate NK ability to control HCV infection, we analyzed healthy donor and HCV-infected donor NK-cell cytolytic activity directed at HCV-infected target cells.Results.HCV-infected subjects’ natural cytotoxicity receptor (NCR)–dependent NK-cell cytolytic activity directed at HCV-infected and uninfected Huh7.5 target cells was greater than that of cells from healthy donors, and this localized to the African American subset. However, IFN-α–enhanced NK cytolytic function was lower in HCV-infected subjects, again localized mainly to the African American subset. Additionally, whereas HCV-infected Huh7.5 cells were more readily targeted than uninfected cells, the selectivity of cytolytic activity for infected targets was lower during HCV infection and after IFN-α stimulation, and lower selectivity was in part attributable to greater NKp46 expression. Furthermore, cytolytic activity was associated with higher serum aspartate aminotransferase, rs12979860IL28Bgenotype, and in vivo response to pegylated IFN/ribavirin therapy.Conclusions.These data indicate that during chronic HCV infection, race-associated increase in NCR expression andIL28B-associated cytolytic activity may participate in host response to IFN-α–containing HCV therapy.