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建立一个能够发生裂解型 Epstein-Barr 病毒激活的鼻咽癌细胞系。

Establishment of a nasopharyngeal carcinoma cell line capable of undergoing lytic Epstein-Barr virus reactivation.

机构信息

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.

School of Nursing, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.

出版信息

Lab Invest. 2018 Aug;98(8):1093-1104. doi: 10.1038/s41374-018-0034-7. Epub 2018 May 16.

Abstract

Epstein-Barr virus (EBV) infects more than 90% of the adult human population. Undifferentiated nasopharyngeal carcinoma (NPC) is common in Southeast Asia, with a particularly high incidence among southern Chinese. The EBV genome can be detected in practically all cancer cells in undifferentiated NPC. The role of EBV in pathogenesis of undifferentiated NPC remains elusive. NPC cell lines are known to be difficult to establish in culture. The EBV+ve NPC cell lines, even if established in culture, rapidly lost their EBV episomes upon prolonged propagation. At present, the C666-1 NPC cell line, which is defective in lytic EBV reactivation, is the only EBV+ve NPC cell line available for NPC and EBV research. The need to establish new and representative NPC cell lines is eminent for NPC and EBV research. In this study, we report the use of the Rho-associated kinase inhibitor (Y-27632) has facilitated the establishment of a new EBV+ve NPC cell line from an earlier established NPC xenograft, C17. The C17 cell line was tumorigenic in immune-deficient mice (NOD/SCID). It retained the EBV episomes and could be induced to undergo productive lytic reactivation of EBV to generate infectious virus particles. The C17 cell line represents a new investigative tool for NPC and EBV studies. The ability of C17 to undergo lytic reactivation is unique and opens up the opportunity to examine regulation of latent and lytic infection of EBV and their contributions to NPC pathogenesis.

摘要

EB 病毒(EBV)感染超过 90%的成年人口。未分化鼻咽癌(NPC)在东南亚很常见,尤其是在中国南方地区发病率较高。EBV 基因组几乎可以在所有未分化 NPC 癌细胞中检测到。EBV 在未分化 NPC 发病机制中的作用仍不清楚。NPC 细胞系在培养中难以建立。即使在培养中建立了 EBV+ve NPC 细胞系,它们也会在长时间繁殖后迅速失去 EBV 外显子。目前,唯一可用于 NPC 和 EBV 研究的 EBV+ve NPC 细胞系是 C666-1 NPC 细胞系,该细胞系在裂解 EBV 重新激活方面存在缺陷。为了 NPC 和 EBV 的研究,建立新的、有代表性的 NPC 细胞系是当务之急。在这项研究中,我们报告了使用 Rho 相关激酶抑制剂(Y-27632)有助于从早期建立的 NPC 异种移植 C17 中建立新的 EBV+ve NPC 细胞系。C17 细胞系在免疫缺陷小鼠(NOD/SCID)中具有致瘤性。它保留了 EBV 外显子,并可诱导其发生 EBV 的产生活性裂解再激活,产生感染性病毒颗粒。C17 细胞系代表了 NPC 和 EBV 研究的一种新的研究工具。C17 进行裂解再激活的能力是独特的,为研究 EBV 的潜伏和裂解感染的调节及其对 NPC 发病机制的贡献提供了机会。

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