20 kDa蛋白（ISG20）的干扰素刺激基因降解乙型肝炎病毒的RNA的

StephenW

Oncotarget. 2016 Sep 8. doi: 10.18632/oncotarget.11907. [Epub ahead of print]
Interferon-stimulated gene of 20 kDa protein (ISG20) degrades RNA of Hepatitis B virus to impede the replication of HBV in vitro and in vivo.Leong CR1,2, Funami K1, Oshiumi H1,3, Mengao D1, Takaki H1, Matsumoto M1, Aly HH4, Watashi K4, Chayama K5, Seya T1.
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AbstractHepatitis B virus (HBV) barely induces host interferon (IFN)-stimulated genes (ISGs), which allows efficient HBV replication in the immortalized mouse hepatocytes as per human hepatocytes. Here we found that transfection of Isg20 plasmid robustly inhibits the HBV replication in HBV-infected hepatocytes irrespective of IRF3 or IFN promoter activation. Transfection of Isg20 is thus effective to eradicate HBV in the infected hepatocytes. Transfection of HBV genome or ε-stem of HBV pgRNA (active pgRNA moiety) failed to induce Isg20 in the hepatocytes, while control polyI:C (a viral dsRNA analogue mimic) activated MAVS pathway leading to production of type I IFN and then ISGsg20 via the IFN-α/β receptor (IFNAR). Consistently, addition of IFN-α induced Isg20 and partially suppressed HBV replication in hepatocytes. Chasing HBV RNA, DNA and proteins by blotting indicated that ISG20 expression decreased HBV RNA and replicative DNA in HBV-transfected cells, which resulted in low HBs antigen production and virus titer. The exonuclease domains of ISG20 mainly participated in HBV-RNA decay. In vivo hydrodynamic injection, ISG20 was crucial for suppressing HBV replication without degrading host RNA in the liver. Taken together, ISG20 acts as an innate anti-HBV effector that selectively degrades HBV RNA and blocks replication of infectious HBV particles. ISG20 would be a critical effector for ameliorating chronic HBV infection in the IFN therapy.


KEYWORDS: ISG20; gene therapy; hepatitis b virus (HBV); interferon (IFN); interferon-stimulated genes (ISGs)

PMID:27626689DOI:10.18632/oncotarget.11907

StephenW

Oncotarget。 2016年8月DOI：10.18632 / oncotarget.11907。 [打印EPUB提前]
20 kDa蛋白（ISG20）的干扰素刺激基因降解乙型肝炎病毒的RNA的阻碍病毒复制在体外和体内。
丰隆CR1,2，Funami K1，Oshiumi H1,3，Mengao D1，高木H1，松本M1，阿里HH4，渡K4，K5茶山，塞牙T1。
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抽象

乙型肝炎病毒（HBV）勉强诱导宿主干扰素（IFN）刺激的基因（的ISG），它允许高效HBV复制的永生化小鼠肝细胞按人肝细胞。在这里，我们发现，Isg20质粒转染有力抑制HBV感染的肝细胞，不论IRF3或干扰素启动子激活HBV复制。 Isg20染因此有效地将感染的肝细胞消灭乙肝病毒。乙肝病毒基因组或HBV pgRNA（主动pgRNA部分）的ε-干转染不能诱导Isg20于肝细胞，而对照聚肌胞：C（病毒双链RNA模拟模拟）激活MAVS途径，导致生产的I型干扰素，然后ISGsg20通过的IFN-α/β受体（IFNAR）。一致，除了IFN-α的诱导Isg20和肝细胞中部分抑制乙型肝炎病毒复制。追HBV的RNA，通过印迹DNA和蛋白质表明ISG20表达降低的HBV RNA和复制的DNA中HBV转染的细胞，这导致了低HBs抗原的生产和病毒滴度。 ISG20的核酸外切酶结构域主要参与HBV-RNA降解。体内高压注射，ISG20是用于抑制HBV复制，而不在肝降解宿主RNA的关键。总之，ISG20作为一个天生的抗HBV效应选择性降低感染乙肝病毒颗粒的HBV RNA和块复制。 ISG20是在干扰素治疗改善慢性HBV感染的关键效应。
关键词：

ISG20;基因治疗;乙肝病毒（HBV）;干扰素（IFN）;干扰素刺激基因（的ISG）

结论：
    27626689
DOI：
    10.18632 / oncotarget.11907

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    1Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638 Japan.
    2Present address: Section of Bioengineering Technology, Universiti Kuala Lumpur (UNIKL) MICET, Kuala Lumpur, 78000 Malaysia.
    3Present address: Department of Immunology, Graduate School of Medical Science, Kumamoto University, Kumamoto, 860-8556 Japan.
    4Department of Virology II, National Institute of Infectious Diseases, Tokyo, 162-8640 Japan.
    5Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553 Japan.