了解对乙型肝炎病毒的免疫反应

StephenW

Public Release: 24-Nov-2016
                                    Understanding immune reaction to the hepatitis B virus                                                

Kumamoto University

   

            
  
  
              
  IMAGE: (A) Infection and tissue sampling timeline. (B & C) Heatmaps of all genes expressed in the liver after HBV infection as assessed by a next-generation sequencer. Upregulated genes are shown...     view more
  

Credit: Professor Hiroyuki Oshiumi

                      The innate immune system in mammals defends against infection from viruses and other microbial infections. Unfortunately, the human immune response to the hepatitis B virus (HBV) is not yet fully understood. Without vaccination, hepatitis B causes both acute and chronic infections of the liver, and can lead to the development of cirrhosis and liver cancer. To gain a deeper understanding of how the immune system reacts to HBV, researchers from several institutions in Japan and Malaysia led by Professor Hiroyuki Oshiumi of Kumamoto University performed in vivo experiments on the tree shrew, a small mammal that is also prone to HBV infection.
        Infection was successful in just over half (55%) of the animals injected with the virus suggesting that a large portion of tree shrews have a natural immunity to HBV. The cytokine interferon-gamma (IFN-gamma), which plays an important role in the activation and modulation of the immune system and in impeding the ability of a virus to replicate, was found early (1 day after infection) in the infected population. This is thought to be caused by the activation of hepatic natural killer (NK) cells in reaction to HBV infection. Further analysis added to the growing body of evidence supporting claims of antiviral actions of IFN-gamma on HBV by confirming that IFN-gamma prompts hepatocyte expression of the DDX60 gene. Expression of this gene causes the degeneration of HBV RNA.
        Importantly, the researchers also found that extracellular vesicles (EV) are integral to the innate immune response to HBV infection. "We showed that EVs coming from HBV-infected hepatocytes carry viral nucleic acids which, in turn, stimulates the innate immune response against HBV," said Professor Oshiumi. "However, we also found that HBV can escape the immune response by increasing the immunosuppressive microRNA levels in exosomes. The increase of these microRNAs eventually results in a reduction of NK cell activation which allows HBV to easily proliferate."
        The results of this research opens a new window into the innate immune response to the hepatitis B virus and provides further insight into the molecular mechanisms involved. The full article can be found online in the open-access journal Frontiers in Immunology.

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        [Citation]
T. Kouwaki, Y. Fukushima, T. Daito, T. Sanada, N. Yamamoto, E. J. Mifsud, C. R. Leong, K. Tsukiyama-Kohara, M. Kohara, M. Matsumoto, T. Seya, and H. Oshiumi, "Extracellular vesicles including exosomes regulate innate immune responses to hepatitis B virus infection," Frontiers in Immunology, vol. 7, p. 335, Aug 2016.
DOI: 10.3389/fimmu.2016.00335


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StephenW

公开发布：2016年11月24日
了解对乙型肝炎病毒的免疫反应

熊本大学
图片

图像：（A）感染和组织取样时间表。 （B＆C）HBV感染后在肝脏中表达的所有基因的热图，由下一代测序仪评估。

信息：Hiroyuki Oshiumi教授

哺乳动物的先天免疫系统防御病毒和其他微生物感染的感染。不幸的是，对乙型肝炎病毒（HBV）的人类免疫反应尚未完全了解。没有接种疫苗，乙型肝炎会引起肝脏的急性和慢性感染，并可导致肝硬化和肝癌的发展。为了更深入地了解免疫系统对HBV的反应，来自熊本大学的Hiroyuki Oshiumi教授在日本和马来西亚的几个机构的研究人员对树犁Shrew，一种也很容易感染HBV的小型哺乳动物进行体内实验。

感染成功了刚刚超过一半（55％）的注射了病毒的动物，表明大部分的树s具有对HBV的天然免疫。在受感染的人群中早期（感染后1天）发现了细胞因子干扰素-γ（IFN-γ），其在免疫系统的激活和调节以及阻止病毒复制的能力中起重要作用。这被认为是由肝自然杀伤（NK）细胞的激活引起的进一步分析加入越来越多的证据支持IFN-γ的抗病毒作用的证据，证实IFN-γ促进DDX60的肝细胞表达基因。该基因的表达引起HBV RNA的变性。

“重要的是，研究人员还发现，胞外囊泡（EV）是对HBV感染的先天免疫反应的一部分。我们发现来自HBV感染的肝细胞的EV携带病毒核酸，其反过来刺激针对HBV的先天免疫应答，“Oshiumi教授说。然而，我们还发现，HBV可以通过增加外来体中的免疫抑制性微RNA水平逃避免疫应答。这些microRNA的增加最终导致NK细胞活化的减少，其允许HBV容易地增殖。

这项研究的结果打开了对乙型肝炎病毒的先天免疫反应的新窗口，并提供进一步洞察所涉及的分子机制。完整的文章可以在开放访问期刊“免疫学前沿”中找到。

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[引用]

T.Kouwaki，Y.Fukushima，T.Daito，T.Sanada，N.Yamamoto，EJMifsud，CRLeong，K.Tsukiyama-Kohara，M.Kohara，M.Matsumoto，T.Seyya和H.Oshiumi，Extracellular囊泡包括调节针对乙型肝炎病毒感染的先天免疫应答的外来体“，Frontiers in Immunology，第7卷，第335页，2016年8月。
DOI：10.3389 / fimmu.2016.00335

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