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塞来昔布通过抑制p38丝裂原活化蛋白激酶(p38 MAPK)的激活下调RTA表达,从而抑制卡波西肉瘤相关疱疹病毒的裂解激活。

Celecoxib Inhibits the Lytic Activation of Kaposi's Sarcoma-Associated Herpesvirus through Down-Regulation of RTA Expression by Inhibiting the Activation of p38 MAPK.

作者信息

Chen Jungang, Jiang Liangyu, Lan Ke, Chen Xulin

机构信息

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 43001, Hubei, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Viruses. 2015 May 5;7(5):2268-87. doi: 10.3390/v7052268.

Abstract

Kaposi's sarcoma associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). KSHV's lytic replication cycle is critical for the pathogenesis of KSHV-associated diseases. Despite recent progress in the development of treatments for KSHV associated malignancies, these therapies are not completely efficacious and cause side effects. Therefore, more effective therapies with antiviral agents against KSHV are urgently needed. In this study, we identified celecoxib as an antiviral agent against KSHV. Our data suggest that celecoxib inhibits the lytic activation of KSHV through the down-regulation of the expression of the lytic switch protein, replication and transcription activator (RTA), by inhibiting the activation of p38 MAPK. Therefore, celecoxib may provide a candidate inhibitor for the therapeutic research of KSHV-related malignancies.

摘要

卡波西肉瘤相关疱疹病毒(KSHV)是卡波西肉瘤(KS)、原发性渗出性淋巴瘤(PEL)和多中心Castleman病(MCD)的病原体。KSHV的裂解复制周期对于KSHV相关疾病的发病机制至关重要。尽管最近在开发针对KSHV相关恶性肿瘤的治疗方法方面取得了进展,但这些疗法并不完全有效,且会引起副作用。因此,迫切需要更有效的抗KSHV抗病毒药物疗法。在本研究中,我们确定塞来昔布为一种抗KSHV的抗病毒药物。我们的数据表明,塞来昔布通过抑制p38丝裂原活化蛋白激酶(p38 MAPK)的激活,下调裂解开关蛋白、复制和转录激活因子(RTA)的表达,从而抑制KSHV的裂解激活。因此,塞来昔布可能为KSHV相关恶性肿瘤的治疗研究提供一种候选抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5222/4452905/22ea95c49783/viruses-07-02268-g001.jpg

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