Niclosamide inhibits lytic replication of Epstein-Barr virus by disrupting mTOR activation
Niclosamide inhibits lytic replication of Epstein-Barr virus by disrupting mTOR activation
复制标题
Niclosamide 通过破坏 mTOR 激活来抑制 Epstein-Barr 病毒的裂解性复制
DOI：
10.1016/j.antiviral.2016.12.002
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发表时间：
2017-02-01
影响因子：
7.6
通讯作者：
Kuang, Ersheng
中科院分区：
文献类型：
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作者：
Huang, Lu;Yang, Mengtian;Kuang, Ersheng
致癌性γ-疱疹病毒Epstein-Barr病毒（EBV）和卡波西肉瘤相关疱疹病毒（KSHV）的感染在人类中引起几种严重的恶性肿瘤。抑制EBV和KSHV的裂解性复制消除了持续感染和传播的储库，从而防止了来自感染源的疾病的发生。抗病毒药物在控制这些病毒性传染病方面受到限制。在这里，我们证明了氯硝柳胺，一个老的驱虫药，抑制mTOR激活在EBV裂解复制。因此，氯硝柳胺有效抑制EBV感染的淋巴瘤细胞和上皮细胞中EBV裂解基因表达、病毒DNA裂解复制和病毒体产生。氯硝柳胺表现出对淋巴瘤细胞的细胞毒性，并在裂解性EBV感染的细胞中诱导不可逆的细胞周期阻滞。mTOR的异位过表达逆转了氯硝柳胺对EBV裂解性复制的抑制作用。类似地，氯硝柳胺抑制KSHV裂解复制。因此，我们得出结论，氯硝柳胺是一个很有前途的候选化疗对急性发生和传播的致癌性γ-疱疹病毒感染性疾病。(C)2016爱思唯尔B. V.保留所有权利。
Infection with the oncogenic y-herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) cause several severe malignancies in humans. Inhibition of the lytic replication of EBV and KSHV eliminates the reservoir of persistent infection and transmission, consequently preventing the occurrence of diseases from the sources of infection. Antiviral drugs are limited in controlling these viral infectious diseases. Here, we demonstrate that niclosamide, an old anthelmintic drug, inhibits mTOR activation during EBV lytic replication. Consequently, niclosamide effectively suppresses EBV lytic gene expression, viral DNA lytic replication and virion production in EBV-infected lymphoma cells and epithelial cells. Niclosamide exhibits cytotoxicity toward lymphoma cells and induces irreversible cell cycle arrest in lytically EBV-infected cells. The ectopic overexpression of mTOR reverses the inhibition of niclosamide in EBV lytic replication. Similarly, niclosamide inhibits KSHV lytic replication. Thus, we conclude that niclosamide is a promising candidate for chemotherapy against the acute occurrence and transmission of infectious diseases of oncogenic y-herpesviruses. (C) 2016 Elsevier B.V. All rights reserved.