5′-triphosphate-siRNA逆转HBV诱导的NK细胞功能低下的机制研究

NK细胞发挥重要的抗病毒效应。然而，HBV感染可导致NK细胞功能下降，其机制尚不十分清楚。我们前期研究证明，兼具靶基因沉默作用和免疫激活作用的5′-triphosphate-HBx-siRNA可通过活化RIG-I信号通路激活肝细胞中的天然免疫应答，从而发挥有效的抗HBV效应。本研究拟在此研究基础上，以NK细胞和HBV小鼠为研究模型，利用分子生物学和细胞生物学技术，分析HBV感染介导NK细胞功能低下的机制；通过体内外实验证实5′-triphosphate-HBx-siRNA活化肝细胞后，诱导分泌细胞因子，进而激活肝脏NK细胞，发挥更有效的抗病毒效应，为更合理地设计HBV治疗方案提供依据。

NK cells exert important anti-viral effects. However, the function of NK cells was impaired during HBV infection, and the mechanisms of dysfunction of NK cell were not well understood yet. Our previous study demonstrated that 5′-triphosphate-HBx-siRNA may not only directly inhibit HBV replication, but also stimulate innate immunity against HBV in hepatocytes. This subject intends to investigate whether NK cells within the liver respond to immune stimulations induced by 3p-siRNA and the the impaired function of NK cells is reversed. Bifunctional siRNAs with both gene-silencing and innate immune-activation properties represent a new potential strategy for the treatment of viral infection.