Expression of Epstein-Barr virus lytic gene BRLF1 in nasopharyngeal carcinoma: potential use in diagnosis
Expression of Epstein-Barr virus lytic gene BRLF1 in nasopharyngeal carcinoma: potential use in diagnosis
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DOI：
10.1099/0022-1317-81-10-2417
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发表时间：
2000-10-01
影响因子：
3.8
通讯作者：
Hu, H
中科院分区：
文献类型：
--
作者：
Feng, P;Ren, EC;Hu, H
未分化鼻咽癌 (NPC) 的肿瘤细胞始终带有 Epstein-Barr 病毒 (EBV) 基因。与 EBV 潜伏期相关的 mRNA 转录物的表达已在此类细胞中得到证实。然而，EBV 裂解基因的表达尚未得到很好的阐明，尽管各种证据表明 NPC 肿瘤细胞中存在 EBV 复制，我们通过 RT-PCR 在从 NPC 和对照个体获得的鼻咽活检中研究了代表性 EBV 裂解基因的 mRNA 表达。在 NPC 和对照活检中，很容易检测到 EBV 裂解基因 BZLF1、BALF2 和 BCLF1。然而，BRLF1 仅在鼻咽癌活检中检测到。然后在体外克隆并表达BRLF1基因，并以蛋白产物Rta为抗原，通过免疫沉淀法检测鼻咽癌患者和健康对照血浆样本中的特异性抗体。在 53 个鼻咽癌血浆样本中的 44 个（83.0%）中检测到针对 Rta 的 IgG 抗体，但仅在 53 个对照样本中的 1 个（1.9%）中检测到。此外，在Rta的C端三分之二处发现了抗体结合区，该血清学结果间接证实了BRLF1在鼻咽癌肿瘤细胞中特异性表达。考虑到 Rta 在 EBV 复制和细胞周期中的多种功能，它可能在 NPC 发病机制中发挥重要作用。此外，针对 Rta 的 IgG 抗体的检测可开发为鼻咽癌的诊断参数。
Tumour cells of undifferentiated nasopharyngeal carcinoma (NPC) consistently harbour Epstein-Barr virus (EBV) genes. Expression of mRNA transcripts associated with EBV latency has been demonstrated in such cells. However, expression of EBV lytic genes has not been well elucidated, although various lines of evidence have suggested that there is EBV replication in NPC tumour cells, We have studied mRNA expression of representative EBV lytic genes by RT-PCR in nasopharynx biopsies obtained from NPC and control individuals. In both NPC and control biopsies, EBV lytic genes BZLF1, BALF2 and BCLF1 were detected readily. However, BRLF1 was detected in NPC biopsies only. The BRLF1 gene was then cloned and expressed in vitro, and the protein product, Rta, was used as an antigen to detect specific antibodies by immunoprecipitation in plasma samples obtained from NPC patients and healthy controls. IgG antibodies directed against Rta were detected in 44 of 53 NPC plasma samples (83.0%), but only in 1 of 53 control samples (1.9%). Furthermore, the antibody binding regions were found in the C-terminal two-thirds of Rta, This serological result confirms indirectly that BRLF1 is specifically expressed in NPC tumour cells. Rta might play;an important role in NPC pathogenesis, considering its multiple functions in EBV replication and cell cycles. Moreover, the detection of IgG antibodies directed against Rta could be developed into a diagnostic parameter for NPC.