HBV DNA聚合酶通过CREB1-HOTTIP-HOXA13轴抑制病毒复制。

StephenW

Hepatology. 2020 Apr 20. doi: 10.1002/hep.31284. [Epub ahead of print]
HBV DNA polymerase restrains viral replication via the CREB1-HOTTIP-HOXA13 axis.
Zhao X1, Fan H1, Chen X1, Zhao X1, Wang X1, Feng Y1, Liu M1, Li S2, Tang H1.
Author information

1
    Tianjin Life Science Research Center, Tianjin Key Laboratory of Inflammation Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
2
    State Key Laboratory of Oncology in Southern China, Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China.

Abstract

LncRNAs have been associated with infection and hepatitis B virus (HBV)-related diseases, though the underlying mechanisms remain unclear. We obtained HBV-HCC lncRNA profiles by deep sequencing and found HOTTIP to be significantly upregulated. RT-qPCR indicated that HOTTIP is highly expressed in HBV-positive hepatoma tissue and induced by HBV in vitro. Virological experiments showed that HOTTIP significantly suppresses the generation of hepatitis B viral surface antigen (HBsAg), hepatitis B viral e antigen (HBeAg) and HBV replication. HOXA13, a downstream factor of HOTTIP, was found to bind to HBV Enh I/Xp to repress the production of HBV pregenome RNA (pgRNA) and total RNA as well as HBV replication, suggesting that HOXA13 mediates HOTTIP-induced suppression of HBV replication. More interestingly, HBV DNA pol binds to and stabilizes CREB1 mRNA to facilitate translation of the protein, which in turn binds to the regulatory element of HOTTIP to promote its expression. CONCLUSION: Our findings demonstrate that HBV DNA pol attenuates HBV replication via activation of the CREB1-HOTTIP-HOXA13 axis. These findings shed light on the mechanism by which HBV restrains replication to contribute to persistent infection.

This article is protected by copyright. All rights reserved.
KEYWORDS:

HBeAg; HBsAg; lncRNA; pgRNA; viral replication

PMID:
    32314410
DOI:
    10.1002/hep.31284

StephenW

肝病学。 2020年4月20日。doi：10.1002 / hep.31284。 [Epub提前发行]
HBV DNA聚合酶通过CREB1-HOTTIP-HOXA13轴抑制病毒复制。
赵X1，范H1，陈X1，赵X1，王X1，冯Y1，刘M1，李S2，唐H1。
作者信息

1个
天津生命科学研究中心，天津市炎症生物学重点实验室，天津市医学表观遗传学协同创新中心，天津医科大学基础医学院病原生物学教研室，天津
2
中山大学肿瘤防治中心肝胆肿瘤科，华南肿瘤学国家重点实验室，广州

抽象

LncRNA与感染和乙型肝炎病毒（HBV）相关疾病有关，尽管其潜在机制尚不清楚。我们通过深度测序获得了HBV-HCC lncRNA图谱，并发现HOTTIP被显着上调。 RT-qPCR表明HOTTIP在HBV阳性肝癌组织中高表达，并在体外被HBV诱导。病毒学实验表明，HOTTIP可显着抑制乙型肝炎病毒表面抗原（HBsAg），乙型肝炎病毒e抗原（HBeAg）和HBV复制的产生。发现HOXA13是HOTTIP的下游因子，它与HBV Enh I / Xp结合以抑制HBV前基因组RNA（pgRNA）和总RNA以及HBV复制的产生，这表明HOXA13介导HOTTIP诱导的HBV复制抑制。更有趣的是，HBV DNA pol结合并稳定CREB1 mRNA以促进蛋白质的翻译，而蛋白质反过来又与HOTTIP的调控元件结合以促进其表达。结论：我们的研究结果表明，HBV DNA pol通过激活CREB1-HOTTIP-HOXA13轴来减弱HBV复制。这些发现阐明了HBV抑制复制从而导致持续感染的机制。

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关键字：

乙肝抗原乙肝表面抗原lncRNA; pgRNA;病毒复制

PMID：
32314410
DOI：
10.1002 /说明31284

乙肝人1949

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