柔红霉素是一种拓扑异构酶II毒物，通过诱导cGAS依赖的先天

StephenW

Biochem Biophys Res Commun. 2018 Sep 9. pii: S0006-291X(18)31895-3. doi: 10.1016/j.bbrc.2018.08.195. [Epub ahead of print]
Daunorubicin, a topoisomerase II poison, suppresses viral production of hepatitis B virus by inducing cGAS-dependent innate immune response.
Imai H1, Dansako H2, Ueda Y1, Satoh S1, Kato N1.
Author information

1
    Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
2
    Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. Electronic address: [email protected].

Abstract

Hepatitis B virus (HBV) causes hepatic diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. These diseases are closely associated with persistent HBV infection. To prevent the progression of hepatic diseases, it is thus important to suppress persistent HBV infection. Daunorubicin (DNR), a topoisomerase II (Top II) poison, is a clinically used anticancer agent with a wide spectrum of activity against malignancies. DNR was recently reported to cause DNA damage-dependent interferon (IFN)-β induction through exogenous cyclic GMP-AMP synthetase (cGAS) and subsequently to suppress Ebola virus replication. In the present study, we demonstrated that DNR caused the inhibition of cell proliferation, but not cell death, through the DNA damage response in immortalized human hepatocyte NKNT-3/NTCP cells. Interestingly, DNR triggered the endogenous cGAS-dependent innate immune response and subsequently suppressed viral production of HBV in NKNT-3/NTCP cells. Top II poisons may be anti-HBV drug candidates.
KEYWORDS:

Cyclic GMP-AMP synthetase; DNA damage response; Daunorubicin; Hepatitis B virus; Innate immune response; Topoisomerase II poison

PMID:
    30209005
DOI:
    10.1016/j.bbrc.2018.08.195

StephenW

Biochem Biophys Res Commun。 2018年9月9日.pii：S0006-291X（18）31895-3。 doi：10.1016 / j.bbrc.2018.08.195。 [提前打印]
柔红霉素是一种拓扑异构酶II毒物，通过诱导cGAS依赖的先天免疫反应来抑制乙型肝炎病毒的病毒产生。
Imai H1，Dansako H2，Ueda Y1，Satoh S1，Kato N1。
作者信息

1
    冈山大学肿瘤病毒学系，日本冈山市北区Shikata-cho 2-5-1，医学，牙科和药学研究科，700-8558。
2
    冈山大学肿瘤病毒学系，日本冈山市北区Shikata-cho 2-5-1，医学，牙科和药学研究科，700-8558。电子地址：[email protected]。

抽象

乙型肝炎病毒（HBV）引起肝病，如慢性肝炎，肝硬化和肝细胞癌。这些疾病与持续的HBV感染密切相关。因此，为了防止肝病的进展，抑制持续性HBV感染是重要的。柔红霉素（DNR）是一种拓扑异构酶II（Top II）毒物，是临床上使用的抗癌剂，具有广泛的抗恶性肿瘤活性。最近报道DNR通过外源性环GMP-AMP合成酶（cGAS）引起DNA损伤依赖性干扰素（IFN）-β诱导，并随后抑制埃博拉病毒复制。在本研究中，我们证明DNR通过永生化人肝细胞NKNT-3 / NTCP细胞中的DNA损伤反应引起细胞增殖的抑制而非细胞死亡。有趣的是，DNR触发了内源性cGAS依赖的先天免疫反应，随后抑制了NKNT-3 / NTCP细胞中HBV的病毒产生。 Top II毒药可能是抗HBV候选药物。
关键词：

环GMP-AMP合成酶; DNA损伤反应;柔红霉素;乙型肝炎病毒;先天免疫反应;拓扑异构酶II毒药

结论：
    30209005
DOI：