Cyno-EBV (EBV-related herpesvirus from cynomolgus macaques) induces rabbit malignant lymphomas and their tumor cell lines frequently show specific chromosomal abnormalities.
Cyno-EBV (EBV-related herpesvirus from cynomolgus macaques) induces rabbit malignant lymphomas and their tumor cell lines frequently show specific chromosomal abnormalities.
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Cyno-EBV（来自食蟹猴的EBV相关疱疹病毒）可诱导兔恶性淋巴瘤，其肿瘤细胞系经常表现出特定的染色体异常。
DOI：
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发表时间：
1999
期刊：
影响因子：
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通讯作者：
T. Akagi
中科院分区：
文献类型：
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作者：
K. Hayashi;H. L. Chen;H. Yanai;T. Koirala;N. Ohara;N. Teramoto;T. Oka;T. Yoshino;K. Takahashi;K. Miyamoto;K. Fujimoto;Y. Yoshikawa;T. Akagi
报道了EB病毒相关食蟹疱疹病毒(Cyno-EBV)诱发兔恶性淋巴瘤(ML)的实验研究。静脉接种产Cyno-EBV猴(食蟹猴)淋巴细胞系(ts-B6)的30只兔中，有27只(90%)在接种后45~115天内发生ML。口服TS-B6细胞后，仅有2只(20%)兔(75~85天)出现ML。注射TS-B6培养的无细胞颗粒的6只兔中有5只(83%)也发生了ML(27-122天)。在接种ts-B6的兔血清中也检测到对EB病毒衣壳抗原的抗体应答。大细胞或混合型ML广泛分布于多个器官，常累及脾、肝、肾、心脏，少数累及肺、淋巴结、脑、眼、胃肠道、胸腺和骨髓。对从荷瘤兔身上建立的五个淋巴瘤细胞系的染色体分析揭示了兔的核型。其中3个细胞系出现12q-或t(7p+：12q-)染色体异常。通过原位杂交和免疫荧光试验，分别在TS-B6细胞、肿瘤组织和所有兔细胞系中表达了EBV编码的小RNA-1和EBV相关核抗原1。通过聚合酶链式反应和Southern印迹分析，在TS-B6细胞和兔淋巴瘤细胞系中也检测到EBV DNA。EBV末端的Southern杂交显示，在Cyno-EBV诱导的兔淋巴瘤中有寡克隆条带。接种B95-8(EBV-产生细胞)或正常食蟹外周血白细胞(对照组)均未诱发淋巴瘤。这些数据表明，兔淋巴瘤的高诱发率可能不是由人EBV(B95-8)引起的，而是由TS-B6细胞的Cyno-EBV引起的。对Cyno-EBV的IR1(BamHIW)区的序列分析表明，该区域与猕猴疱疹病毒1的BamHIW区非常相似，后者是艾滋病相关淋巴瘤猴子模型的病原体。本实验建立的具有特异性染色体异常的兔淋巴瘤模型有助于阐明EBV在人类EBV相关淋巴瘤中的作用，为研究其防治方案提供了一种新的手段。
Malignant lymphoma (ML) induction in rabbits by Epstein-Barr virus (EBV)-related herpesvirus of cynomolgus (Cyno-EBV) is reported. Twenty-seven of 30 (90%) rabbits inoculated intravenously with Cyno-EBV-producing simian (cynomolgus) lymphocyte cell line (Ts-B6) cells developed ML between 45 and 115 days after inoculation. The peroral inoculation of Ts-B6 cells induced ML in only 2 of 10 (20%) rabbits (75 to 85 days). Five of 6 (83%) rabbits injected with cell-free pellets from Ts-B6 cultures also developed ML (27 to 122 days). Antibody response to the viral capsid antigen of EBV was also detected in sera from rabbits inoculated with Ts-B6. ML of the large cell or mixed type infiltrated diffusely in many organs, frequently involving the spleen, liver, kidneys, heart, and less frequently the lungs, lymph nodes, brain, eyes, gastrointestinal tract, thymus, and bone marrow. A chromosomal analysis of five lymphoma cell lines established from tumor-bearing rabbits revealed the rabbit karyotype. Three of these cell lines showed the chromosomal abnormalities with 12q- or t (7p+:12q-). EBV-encoded small RNA-1 and EBV-associated nuclear antigen 1 were expressed in Ts-B6 cells, the tumor tissues, and all rabbit cell lines by in situ hybridization and by immunofluorescence tests, respectively. EBV DNA was also detected in Ts-B6 cells and rabbit lymphoma cell lines by polymerase chain reaction and Southern blot analysis. The Southern blots of EBV termini revealed oligoclonal bands in the Cyno-EBV-induced rabbit lymphomas. No lymphoma was induced by the inoculation of B95-8 (EBV-producing cells) or peripheral leukocytes from normal cynomolgus (controls). These data suggest that the high rate of lymphoma induction in rabbits may be caused not by human EBV (B95-8) but by Cyno-EBV from Ts-B6 cells. A sequence analysis of the IR1 (BamHIW) region of Cyno-EBV revealed that this region is quite similar to that of herpesvirus Macaca fascicularis 1, which is a causative agent for a monkey model of AIDS-related lymphomas. The present rabbit model of lymphoma with specific chromosomal abnormalities is very useful to clarify the role of EBV in human EBV-associated lymphoma and provides a means for studying prophylactic and therapeutic regimens.