Hayashi K, Teramoto N, Akagi T
Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Histol Histopathol. 2002 Oct;17(4):1293-310. doi: 10.14670/HH-17.1293.
Animal models of human EBV-associated diseases are essential to elucidate the pathogenesis of EBV-associated diseases. Here we review those previous models using EBV or EBV-like herpesviruses and describe the details on 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%) during 2-5 months. EBV-DNA was detected in peripheral blood by PCR from 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 lymphoma cell lines, most of which have specific chromosomal abnormality, showed tumorigenicity in nude mice. The second is the first animal model for EBV-infected T-cell LPD with virus-associated hemophagocytic syndrome (VAHS), using rabbits infected with an 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, during 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.
人类EBV相关疾病的动物模型对于阐明EBV相关疾病的发病机制至关重要。在此，我们回顾以往使用EBV或EBV样疱疹病毒构建的模型，并详细描述我们新开发的两种由猿猴EBV样病毒诱导的兔淋巴增殖性疾病（LPD）模型。第一种是食蟹猴EBV诱导的兔T细胞淋巴瘤，通过静脉注射（77 - 90%）和口服（82 - 89%）接种，持续2 - 5个月。口服接种后2天通过PCR在外周血中检测到EBV - DNA，而抗EBV - VCA IgG在3周后升高。兔淋巴瘤及其细胞系含有EBV - DNA并表达EBV编码的RNA - 1（EBER - 1）。兔淋巴瘤细胞系大多具有特定的染色体异常，在裸鼠中显示出致瘤性。第二种是首个用于EBV感染的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EBV样疱疹病毒猴疱疹病毒（HVP）的兔。静脉注射产生HVP的细胞的兔抗EBV - VCA - IgG滴度升高，大多数（85%）随后在22 - 105天内死于致命的LPD和VAHS，伴有出血和肝脾肿大。对5只兔进行无细胞HVP口腔喷雾诱导病毒感染，5只中有3只发生血清转化，3只感染兔中有2只死于伴有VAHS的LPD。在许多器官中观察到含有HVP - DNA并表达EBER - 1的非典型T淋巴细胞。在淋巴结、脾脏、骨髓和胸腺中观察到噬血细胞组织细胞增生。这些兔模型也是用于研究EBV生物学和发病机制以及预防和治疗方案的有用且廉价的替代实验模型系统。
