乙型肝炎病毒基因组的复制触发在不存在B型肝炎表面抗原的t

StephenW

Hepatitis B virus genome replication triggers toll-like receptor 3-dependent interferon responses in the absence of hepatitis B surface antigen

    Catherine Isabell Real, Mengji Lu, Jia Liu, Xuan Huang, Martin Trippler, Markus Hossbach, Jochen Deckert, Kerstin Jahn-Hofmann, Ludger Markus Ickenstein, Matthias Johannes John, Kathrin Gibbert, Ulf Dittmer, Hans-Peter Vornlocher, Reinhold Schirmbeck, Guido Gerken, Joerg Friedrich Schlaak & Ruth Broering

    Scientific Reports 6, Article number: 24865 (2016)
    doi:10.1038/srep24865
    Download Citation
        Hepatitis BImmune evasion

Received:
    04 January 2016
Accepted:
    06 April 2016
Published online:
    28 April 2016

Abstract

The hepatitis B virus (HBV) has been described as stealth virus subverting immune responses initially upon infection. Impaired toll-like receptor signaling by the HBV surface antigen (HBsAg) attenuates immune responses to facilitate chronic infection. This implies that HBV replication may trigger host innate immune responses in the absence of HBsAg. Here we tested this hypothesis, using highly replicative transgenic mouse models. An HBV replication-dependent expression of antiviral genes was exclusively induced in HBsAg-deficient mice. These interferon responses attributed to toll-like receptor 3 (TLR3)-activated Kupffer and liver sinusoidal endothelial cells and further controlled the HBV genome replication. However, activation of TLR3 with exogenous ligands indicated additional HBs-independent immune evasion events. Our data demonstrate that in the absence of HBsAg, hepatic HBV replication leads to Tlr3-dependent interferon responses in non-parenchymal liver cells. We hypothesize that HBsAg is a major HBV-mediated evasion mechanism controlling endogenous antiviral responses in the liver. Eradication of HBsAg as a therapeutic goal might facilitate the induction of endogenous antiviral immune responses in patients chronically infected with HBV.

StephenW

乙型肝炎病毒基因组的复制触发在不存在B型肝炎表面抗原的toll样受体3依赖性干扰素响应

    凯瑟琳·伊莎贝尔真实，蒙基陆，刘嘉，玄黄，马丁特里普勒，马库斯Hossbach，约亨Deckert，克斯廷雅恩 - 霍夫曼，卢德格尔·马库斯Ickenstein，马蒂亚斯约翰内斯·约翰，席Gibbert，乌尔夫·迪特默，汉斯 - 彼得·Vornlocher，莱因霍尔德Schirmbeck，圭多Gerken，约尔格·弗里德里希Schlaak与露丝Broering

    科学报告6，商品编号：24865（2016）
    DOI：10.1038 / srep24865
    下载文献
        肝炎BImmune逃税

收稿日期：
    2016年1月4日
公认：
    2016年4月6日
网络发布时间：
    2016年4月28日

抽象

乙肝病毒（HBV）已被描述为隐形病毒在感染后最初颠覆免疫应答。由HBV表面抗原（HBsAg）受损toll样受体信号衰减的免疫反应，以促进慢性感染。这意味着HBV复制可能触发在不存在的HBsAg宿主先天免疫反应。在这里，我们测试这个假设，使用高度可复制转基因小鼠模型。抗病毒基因的HBV复制依赖性表达的HBsAg中的缺陷小鼠是专门诱导。归因于toll样受体3（TLR3）这些干扰素的反应活化的库普弗和肝窦内皮细胞，并进一步控制的HBV基因组的复制。然而，用外源性配体的TLR3的活化表明附加HBs抗体无关的免疫逃避的事件。我们的数据表明，在不存在的HBsAg，肝HBV复制导致非实质肝细胞TLR3依赖性干扰素应答。我们推测，乙肝表面抗原是一个重大的HBV介导的规避​​机制控制在肝脏内源性抗病毒反应。的HBsAg根除作为治疗目标可能促进内源性抗病毒免疫应答的慢性感染HBV的患者的诱导。

StephenW

全文:
http://www.nature.com/articles/s ... rtId=OTIwMzMxMjM5S0

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