文章：

Epstein-Barr核抗原1诱导细胞microRNA hsa-miR-127的表达，并损害EB病毒感染的记忆B细胞的B细胞分化。伯基特淋巴瘤发病机制的新见解

Epstein-Barr nuclear antigen 1 induces expression of the cellular microRNA hsa-miR-127 and impairing B-cell differentiation in EBV-infected memory B cells. New insights into the pathogenesis of Burkitt lymphoma

原文发布日期：2012-08-31

DOI: 10.1038/bcj.2012.29

类型: Original Article

开放获取: 是

英文摘要：

Epstein-Barr Virus (EBV) is a γ-herpesvirus that infects >90% of the human population. Although EBV persists in its latent form in healthy carriers, the virus is also associated with several human cancers. EBV is strongly associated with Burkitt lymphoma (BL), even though there is still no satisfactory explanation of how EBV participates in BL pathogenesis. However, new insights into the interplay between viruses and microRNAs (miRNAs) have recently been proposed. In particular, it has been shown that B-cell differentiation in EBV-positive BL is impaired at the post-transcriptional level by altered expression of hsa-miR-127. Here, we show that the overexpression of hsa-miR-127 is due to the presence of the EBV-encoded nuclear antigen 1 (EBNA1) and give evidence of a novel mechanism of direct regulation of the human miRNA by this viral product. Finally, we show that the combinatorial expression of EBNA1 and hsa-miR-127 affects the expression of master B-cell regulators in human memory B cells, confirming the scenario previously observed in EBV-positive BL primary tumors and cell lines. A good understanding of these mechanisms will help to clarify the complex regulatory networks between host and pathogen, and favor the design of more specific treatments for EBV-associated malignancies.

摘要翻译： 

EB病毒（EBV）是一种γ疱疹病毒，感染全球超过90%的人口。虽然EBV在健康携带者体内以潜伏形式持续存在，但该病毒也与多种人类癌症相关。EBV与伯基特淋巴瘤（BL）密切相关，但关于EBV如何参与BL发病机制仍缺乏令人满意的解释。然而，近期研究提出了关于病毒与微小RNA（miRNA）相互作用的新见解。特别是，研究发现EBV阳性BL中B细胞分化在转录后水平受到干扰，这与hsa-miR-127表达改变有关。本文证实hsa-miR-127的过表达源于EBV编码核抗原1（EBNA1）的存在，并揭示了该病毒产物直接调控人类miRNA的新机制。最后，我们证明EBNA1与hsa-miR-127的组合表达会影响人类记忆B细胞中主要B细胞调控因子的表达，这印证了先前在EBV阳性BL原发肿瘤和细胞系中观察到的现象。深入理解这些机制将有助于阐明宿主与病原体之间复杂的调控网络，并为EBV相关恶性肿瘤的特异性治疗设计提供支持。

原文链接：

Epstein-Barr nuclear antigen 1 induces expression of the cellular microRNA hsa-miR-127 and impairing B-cell differentiation in EBV-infected memory B cells. New insights into the pathogenesis of Burkitt lymphoma