Epstein-Barr virus and a cellular signaling pathway in lymphomas from immunosuppressed patients
Epstein-Barr virus and a cellular signaling pathway in lymphomas from immunosuppressed patients
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DOI：
10.1056/nejm199805143382003
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发表时间：
1998-05-14
影响因子：
158.5
通讯作者：
Liebowitz, D
中科院分区：
文献类型：
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作者：
Liebowitz, D
背景。 EB 病毒 (EBV) 与各种恶性和良性淋巴增殖性疾病有关。它还可以在体外有效转化人类 B 淋巴细胞。 EBV 感染细胞的潜伏膜蛋白 1 (LMP1) 在此过程中发挥着核心作用，它模仿肿瘤坏死因子 (TNF) 受体家族的成员，从而通过细胞质 TNF 受体相关因子 (TRAF) 将生长信号从细胞膜传递到细胞核。我在患有移植后淋巴增殖性疾病和与获得性免疫缺陷综合征 (AIDS) 相关的非霍奇金淋巴瘤患者的肿瘤组织中寻找 LMP1 介导的信号转导通过 TRAF 的证据。方法。通过双免疫荧光显微镜和免疫沉淀分析研究了肿瘤组织中 LMP1 与 TRAF-1 或 TRAF-3 的关联。通过核因子-kappa B (NF-kappa B) 转录因子的电泳迁移率变动测定寻找 LMP1-TRAF 信号传导的证据。结果。对来自八名移植后淋巴增殖性疾病患者、两名艾滋病相关非霍奇金淋巴瘤患者和三名地方性伯基特淋巴瘤患者的肿瘤进行了分析。六名患有移植后淋巴组织增生性疾病的患者的肿瘤呈 EBV 阳性并表达 LMP1；两个样本 EBV 呈阴性。两名艾滋病相关非霍奇金淋巴瘤患者的肿瘤均为 EBV 阳性并表达 LMP1，而所有三名伯基特肿瘤患者的肿瘤均为 EBV 阳性但 LMP1 阴性。双免疫荧光显微镜显示，在所有 8 个 EBV 阳性、LMP1 阳性样本中，LMP1 与 TRAF-1 和 TRAF-3 一起定位并免疫沉淀。电泳迁移率变动分析显示，所有 8 个 EBV 阳性、LMP1 阳性样本中均存在激活的 NF-κ B，但在 EBV 阴性、LMP1 阴性样本或 3 个 EBV 阳性、LMP1 阴性样本中均未激活。结论。 LMP1 介导的 TRAF 系统信号传导在免疫抑制患者中出现的 EBV 阳性淋巴瘤的发病机制中发挥作用。 (C) 1998 年，马萨诸塞州医学会。
Background. Epstein-Barr virus (EBV) is associated with various malignant and benign lymphoproliferative disorders. It also efficiently transforms human B lymphocytes in vitro. The latent membrane protein 1 (LMP1) of EBV-infected cells plays a central part in this process by mimicking members of the family of tumor necrosis factor (TNF) receptors, thereby transmitting growth signals from the cell membrane to the nucleus through cytoplasmic TNF-receptor-associated factors (TRAFs). I sought evidence of LMP1-mediated signal transduction through TRAFs in tumor tissue from patients with post-transplantation lymphoproliferative disease and non-Hodgkin's lymphomas related to the acquired immunodeficiency syndrome (AIDS).Methods. The association of LMP1 with TRAF-1 or TRAF-3 in tumor tissue was studied with double-immunofluorescence microscopy and immunoprecipitation assays. Evidence of LMP1-TRAF signaling was sought with an electrophoretic mobility shift assay for the nuclear factor-kappa B (NF-kappa B) transcription factor.Results. Tumors from eight patients with post-transplantation lymphoproliferative disease, two patients with AIDS-associated non-Hodgkin's lymphoma, and three patients with endemic Burkitt's lymphoma were analyzed. Tumors from six of the patients with post-transplantation lymphoproliferative disease were positive for EBV and expressed LMP1; two samples were EBV-negative. Tumors from both patients with AIDS-associated non-Hodgkin's lymphoma were EBV-positive and expressed LMP1, whereas tumors from all three patients with Burkitt's tumors were positive for EBV but negative for LMP1. Double-immunofluorescence microscopy showed that LMP1 localized with and immunoprecipitated with TRAF-1 and TRAF-3 in all eight of the EBV-positive, LMP1-positive samples. An electrophoretic mobility shift assay revealed activated NF-kappa B in all eight EBV-positive, LMP1-positive samples as well, but not in either of the EBV-negative, LMP1-negative samples or in the three EBV-positive, LMP1-negative samples.Conclusions. LMP1-mediated signaling through the TRAF system has a role in the pathogenesis of the EBV-positive lymphomas that arise in immunosuppressed patients. (C) 1998, Massachusetts Medical Society.