Shibata Yukiko, Hoshino Yo, Hara Shinya, Yagasaki Hiroshi, Kojima Seiji, Nishiyama Yukihiro, Morishima Tsuneo, Kimura Hiroshi
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
J Med Virol. 2006 Jun;78(6):770-9. doi: 10.1002/jmv.20622.
Chronic active Epstein-Barr virus (EBV) infection is a severe systemic disease associated with high rates of mortality and morbidity. Recent studies suggest that the clonal expansion of EBV-infected T or natural killer cells plays a crucial role in the pathogenesis of chronic active EBV infection. However, it is not clear whether chronic active EBV infection is truly a monoclonal disorder that originates from one cell. The clonality of EBV was investigated by sequence variation of the latent membrane protein 1 (LMP1) gene, which has a high degree of sequence heterogeneity. Peripheral blood mononuclear cells were obtained from nine Japanese patients with chronic active EBV infection and four with infectious mononucleosis. A carboxyl-terminal region of the LMP1 gene was analyzed by polymerase chain reaction (PCR). The amplified PCR products were subcloned, and 18 clones from each sample were sequenced. Patients with chronic active EBV infection each had two to five different LMP1 nucleotide sequences, whereas patients with infectious mononucleosis each had one to seven different sequences. Patients with chronic active EBV infection and infectious mononucleosis both had one dominant sequence. Longitudinal analysis was performed in four patients with chronic active EBV infection, in whom the dominant strains were found to have remained unchanged for several years. The results suggest that EBV in patients with chronic active EBV infection was polyclonal, although clonal expansion may occur. Collectively, these findings are critical to clarify further the pathogenesis of chronic active EBV infection and aid in the development of effective treatment strategies.
慢性活动性EB病毒（EBV）感染是一种严重的全身性疾病，与高死亡率和高发病率相关。最近的研究表明，EBV感染的T细胞或自然杀伤细胞的克隆性扩增在慢性活动性EBV感染的发病机制中起关键作用。然而，尚不清楚慢性活动性EBV感染是否真的是一种起源于单个细胞的单克隆疾病。通过具有高度序列异质性的潜伏膜蛋白1（LMP1）基因的序列变异来研究EBV的克隆性。从9名日本慢性活动性EBV感染患者和4名传染性单核细胞增多症患者中获取外周血单个核细胞。通过聚合酶链反应（PCR）分析LMP1基因的羧基末端区域。对扩增的PCR产物进行亚克隆，并对每个样品的18个克隆进行测序。慢性活动性EBV感染患者每人有2至5种不同的LMP1核苷酸序列，而传染性单核细胞增多症患者每人有1至7种不同序列。慢性活动性EBV感染患者和传染性单核细胞增多症患者均有一个优势序列。对4名慢性活动性EBV感染患者进行了纵向分析，发现其中的优势菌株在数年中保持不变。结果表明，慢性活动性EBV感染患者的EBV是多克隆的，尽管可能发生克隆性扩增。总的来说，这些发现对于进一步阐明慢性活动性EBV感染的发病机制以及帮助制定有效的治疗策略至关重要。
