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鞘氨醇菌素通过活性氧再激活潜伏状态的 Epstein-Barr 病毒的裂解复制。

Chaetocin reactivates the lytic replication of Epstein-Barr virus from latency via reactive oxygen species.

机构信息

Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China.

出版信息

Sci China Life Sci. 2017 Jan;60(1):66-71. doi: 10.1007/s11427-016-0286-7. Epub 2017 Jan 5.

DOI:10.1007/s11427-016-0286-7
PMID:28063010
Abstract

Oxidative stress, regarded as a negative effect of free radicals in vivo, takes place when organisms suffer from harmful stimuli. Some viruses can induce the release of reactive oxygen species (ROS) in infected cells, which may be closely related with their pathogenicity. In this report, chaetocin, a fungal metabolite reported to have antimicrobial and cytostatic activity, was studied for its effect on the activation of latent Epstein-Barr virus (EBV) in B95-8 cells. We found that chaetocin remarkably up-regulated EBV lytic transcription and DNA replication at a low concentration (50 nmol L). The activation of latent EBV was accompanied by an increased cellular ROS level. N-acetyl-L-cysteine (NAC), an ROS inhibitor, suppressed chaetocin-induced EBV activation. Chaetocin had little effect on histone H3K9 methylation, while NAC also significantly reduced H3K9 methylation. These results suggested that chaetocin reactivates latent EBV primarily via ROS pathways.

摘要

氧化应激被认为是生物体受到有害刺激时体内自由基的一种负面影响。一些病毒可以诱导感染细胞中活性氧物质(ROS)的释放,这可能与其致病性密切相关。在本报告中,研究了真菌代谢产物 chaetocin 对 B95-8 细胞中潜伏性 Epstein-Barr 病毒(EBV)激活的影响,该物质具有抗微生物和细胞抑制活性。我们发现 chaetocin 在低浓度(50 nmol/L)下显著上调 EBV 裂解转录和 DNA 复制。潜伏 EBV 的激活伴随着细胞内 ROS 水平的升高。ROS 抑制剂 N-乙酰-L-半胱氨酸(NAC)抑制 chaetocin 诱导的 EBV 激活。Chaetocin 对组蛋白 H3K9 甲基化几乎没有影响,而 NAC 也显著降低了 H3K9 甲基化。这些结果表明,chaetocin 主要通过 ROS 途径重新激活潜伏性 EBV。

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