Establishment and characterization of a primary effusion (body cavity-based) lymphoma cell line (BC-3) harboring Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in the absence of Epstein-Barr virus

Establishment and characterization of a primary effusion (body cavity-based) lymphoma cell line (BC-3) harboring Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in the absence of Epstein-Barr virus
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DOI:
10.1182/blood.v88.7.2648.bloodjournal8872648
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发表时间:
1996-10-01
期刊:
影响因子:
20.3
通讯作者:
Cesarman, E
Cesarman, E
中科院分区:
医学1区
文献类型:
--
作者:
Arvanitakis, L;Mesri, EA;Cesarman, E

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最近发现的卡波西肉瘤相关疱疹病毒 (KSHV),也称为人类疱疹病毒 8 (HHV-8),被发现与一种不寻常的获得性免疫缺陷综合征相关淋巴瘤亚型一致相关,即所谓的体腔淋巴瘤 (BCBL) 或原发性渗出性淋巴瘤 (PEL)。这些淋巴瘤具有独特的形态学和分子特征,并且以淋巴瘤渗出物的形式生长,没有可识别的连续肿瘤块。到目前为止,由于缺乏适当的模型系统以及在几乎所有检查的病例和所有先前建立的细胞系中同时存在 Epstein-Barr 病毒(EBV),描述 KSHV 在 PEL 发病机制中的作用的努力受到阻碍。我们现在报告了一种新型 PEL 细胞系 BC-3 的建立和表征,该细胞系通过聚合酶链式反应 (PCR) 检测为 KSHV+,但通过多种方法评估为 EBV(-),包括 EBER、EBNA-2 和 EBNA-3C 的 PCR。该细胞系是从 HIV 患者的淋巴瘤渗出液中建立的,具有与 PEL 诊断一致的免疫表型和分子特征,包括不确定的免疫表型具有 B 细胞免疫基因型且缺乏 c-myc 原癌基因重排,脉冲场凝胶电泳显示细胞系和病毒分离物中均具有约 170 kb 的完整 KSHV 基因组,而通过电子显微镜可见疱疹病毒样衣壳。因此,BC-3 细胞系作为 KSHV 的来源是一种宝贵的工具,可用于评估该病毒的致病潜力及其在卡波西肉瘤和恶性淋巴瘤发展中的作用的机制特征。 (C) 1996 年,美国血液学会。
The recently identified Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), has been found to be consistently associated with an unusual subset of acquired immunodeficiency syndrome-related lymphomas, the so-called body cavity-based lymphomas (BCBL) or primary effusion lymphomas (PEL). These lymphomas are characterized by a unique spectrum of morphologic and molecular characteristics, and grow as lymphomatous effusions without an identifiable contiguous tumor mass. Until now, efforts to delineate the role of KSHV in the pathogenesis of PELs have been hampered by the lack of appropriate model systems and the concomitant presence of Epstein-Barr virus (EBV) in nearly ail cases examined, and in all previously established cell lines. We now report the establishment and characterization of a novel PEL cell line, BC-3, which is KSHV+ by polymerase chain reaction (PCR) but EBV(-) as assessed by a variety of methods including PCR for EBER, EBNA-2, and EBNA-3C, This cell line was established from a lymphomatous effusion obtained from an HIV- patient, and has immunophenotypic and molecular features consistent with the diagnosis of PEL, including an indeterminate immunophenotype with a B-cell immunogenotype and lack of c-myc proto-oncogene rearrangements, Pulsed-field gel electrophoresis shows an intact KSHV genome of about 170 kb both in the cell line and in the viral isolate, whereas herpesvirus-like capsids are visible by electron microscopy. Consequently, the BC-3 cell line represents an invaluable tool as a source of KSHV, for both the evaluation of the pathogenic potential of this virus and the mechanistic characterization of its role in the development of Kaposi's sarcoma and malignant lymphoma. (C) 1996 by The American Society of Hematology.