ANIMAL MODEL FOR HUMAN EB VIRUS-RELATED TUMOR: PATHOGENESIS OF RABBIT LYMPHOMA INDUCED BY SIMIAN EBV-RELATED VIRUS

人类ebv相关疾病的动物模型对于阐明ebv感染和ebv相关疾病的发病机制至关重要。本文报道了两种新建立的猴ebv样病毒诱导的兔淋巴细胞增生性疾病（LPD）模型。第一种是2- 5个月后静脉注射（77-90%）和口服（82- 89%）的兔cynomolgus - ebv诱导的t细胞淋巴瘤。口服接种ebv - vca后第2天用PCR检测外周血EBV-DNA，第3周提高抗ebv - vca IgG。兔淋巴瘤及其细胞系含有EBV-DNA并表达ebv -编码RNA-1 （EBER-1）。兔淋巴瘤及其细胞系含有EBV-DNA并表达ebv -编码RNA-1 （EBER-1）。兔淋巴瘤细胞系在裸鼠身上表现出致瘤性，其中一些具有特异性的染色体异常。第二个是第一个也是唯一的ebv感染t细胞LPD伴病毒相关噬血细胞综合征（VAHS）的动物模型，使用感染了狒狒ebv样疱疹病毒，疱疹病毒（HVP）的兔子。静脉注射产生hvp细胞的家兔抗ebv - vca - igg滴度升高，大多数（85%）随后在相对较短的时间（22-105天）内死于致命性LPD和VAHS，并伴有出血和肝脾肿大。经口喷雾无细胞HVP诱导5只家兔中3只发生血清转化感染，2只感染家兔死于LPD伴VAHS。在许多器官中观察到含有HVP-DNA和表达EBER-1的非典型T淋巴细胞。淋巴结、脾脏、骨髓、胸腺均可见噬血细胞增多。这些兔模型也是研究EBV的生物学和发病机制，以及预防和治疗方案，特别是与人类致命性EBV相关的LPD和VAHS相关的有用且廉价的替代实验模型系统。

Animal models of human EBV-associated diseases are essential to elucidate the pathogenesis of EBV-infection and EBV-associated diseases. Here we reported our two newly developed rabbit models of lymphoproliferative diseases (LPD) induced by simian EBV-like viruses. The first is Cynomolgus-EBV-induced T-cell lymphomas in rabbits inoculated intravenously (77-90%) and orally (82- 89%) about 2 -5 months later. EBV-DNA was detected in peripheral blood by PCR since 2 days after oral inoculation while anti-EBV-VCA IgG was raised 3 weeks later. Rabbit lymphomas and their cell lines contained EBV-DNA and expressed EBV-encoded RNA-1 (EBER-1). Rabbit lymphomas and their cell lines contained EBV-DNA and expressed EBV-encoded RNA-1 (EBER-1). Rabbit lymphoma cell lines, some of which have specific chromosomal abnormality, showed tumorigenicity in nude mice. The second is the first and unique animal model for EBV-infected T-cell LPD with virus-associated hemophagocytic syndrome (VAHS) using rabbits infected with the baboon EBV-like herpesvirus, Herpesvirus papio (HVP). Rabbits inoculated intravenously with HVP-producing cells showed increased anti-EBV-VCA-IgG titers, and most (85%) subsequently died of fatal LPD and VAHS, with bleeding and hepatosplenomegaly, within a relatively short time (22-105 days). Peroral spray of cell-free HVP induced viral infection with seroconversion in 3 out of 5 rabbits, with 2 of the 3 infected rabbits dying of LPD with VAHS. Atypical T lymphocytes containing HVP-DNA and expressing EBER-1 were observed in many organs. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. These rabbit models are also useful and inexpensive alternative experimental model systems for studying the biology and pathogenesis of EBV, and prophylactic and therapeutic regimens, especially in relation to human fatal EBV-related LPD and VAHS.