Hayashi K, Ohara N, Teramoto N, Onoda S, Chen H L, Oka T, Kondo E, Yoshino T, Takahashi K, Yates J, Akagi T
Second Department of Pathology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama-city 700-8558, Japan.
Am J Pathol. 2001 Apr;158(4):1533-42. doi: 10.1016/S0002-9440(10)64104-1.
Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis. However, the animal model for EBV-AHS has not been developed. We reported the first animal model for EBV-AHS using rabbits infected with EBV-related herpesvirus of baboon (HVP). Eleven of 13 (85%) rabbits inoculated intravenously with HVP-producing cells developed fatal lymphoproliferative disorders (LPD) between 22 and 105 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11 rabbits. The peroral spray of cell-free HVP induced the virus infection with increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and two of these three infected rabbits died of LPD with HPS. Autopsy revealed hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing EBV-encoded small RNA-1 infiltrated diffusely in many organs, frequently involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by polymerase chain reaction or Southern blot analysis. Reverse transcriptase-polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts, suggesting latency type III infection. These data indicate that the high rate of rabbit LPD with HPS induction is caused by HVP. This system is useful for studying the pathogenesis, prevention, and treatment of human EBV-AHS.
爱泼斯坦-巴尔病毒相关噬血细胞综合征（EBV-AHS）常与致命性传染性单核细胞增多症相关。然而，EBV-AHS的动物模型尚未建立。我们报道了首个使用感染狒狒EBV相关疱疹病毒（HVP）的兔子建立的EBV-AHS动物模型。13只经静脉接种产生HVP的细胞的兔子中有11只（85%）在接种后22至105天内发生了致命性淋巴增殖性疾病（LPD）。这11只兔子中有9只的LPD还伴有噬血细胞综合征（HPS）。对5只兔子进行无细胞HVP经口喷雾，其中3只出现病毒感染，抗EBV病毒衣壳抗原-IgG滴度升高，这3只受感染兔子中有2只死于伴有HPS的LPD。尸检显示肝脾肿大和淋巴结肿大。表达EBV编码小RNA-1的非典型淋巴样T细胞在许多器官中弥漫浸润，常累及淋巴结、脾脏和肝脏。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。通过聚合酶链反应或Southern印迹分析在受感染兔子的组织和外周血中检测到HVP-DNA。逆转录酶-聚合酶链反应显示同时存在HVP-EBNA1和HVP-EBNA2转录本，提示潜伏III型感染。这些数据表明，HVP导致兔子发生LPD并诱导HPS的比率很高。该系统有助于研究人类EBV-AHS的发病机制、预防和治疗。
