Reversal of hepatitis B virus-induced systemic immune tolerance by intrinsic innate immune stimulation

Reversal of hepatitis B virus-induced systemic immune tolerance by intrinsic innate immune stimulation
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通过内在先天免疫刺激逆转乙型肝炎病毒诱导的全身免疫耐受

DOI:
10.1111/jgh.12034
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发表时间:
2013-08-01
影响因子:
4.1
通讯作者:
Tian, Zhigang
Tian, Zhigang
中科院分区:
医学3区
文献类型:
--
作者:
Han, Qiuju;Lan, Peixiang;Tian, Zhigang

文献摘要

被引文献

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慢性B型肝炎病毒(HBV)感染诱导的机体免疫耐受是一个重要的问题,但其机制尚不清楚。在这篇简短的综述中,我们总结了慢性HBV感染中参与免疫耐受的先天性和获得性免疫应答受损。此外,我们描述了一种新的双功能小RNA,以抑制HBV复制和刺激对HBV的先天免疫,这提出了一个有前途的免疫干预中断HBV诱导的免疫耐受。建立了HBV持续存在的小鼠模型,并观察了HBV疫苗免疫耐受的发生情况。化学合成的双功能小RNA(3 p-HBx基因[HBx]-small interfering RNA)体外实验和生物学构建的双功能载体(单链RNA-HBx-短发夹RNA)体内实验均能逆转HBV疫苗免疫耐受。
Systemic immune tolerance induced by chronic hepatitis B virus (HBV) infection is a significant question, but the mechanism of which remains unclear. In this mini-review, we summarize the impaired innate and adaptive immune responses involved in immune tolerance in chronic HBV infection. Furthermore, we delineate a novel dual functional small RNA to inhibit HBV replication and stimulate innate immunity against HBV, which proposed a promising immunotherapeutic intervention to interrupt HBV-induced immunotolerance. A mouse model of HBV persistence was established and used to observe the immune tolerant to HBV vaccination, the cell-intrinsic immune tolerance of which might be reversed by chemically synthesized dual functional small RNA (3p-hepatitis B Virus X gene [HBx]-small interfering RNA) in vitro experiments and by biologically constructed dual functional vector (single-stranded RNA-HBx-short hairpin RNA) in vivo experiment using HBV-carrier mice.