Cell biological analysis of EB virus in EBV associated peripheral T cell lymphoma

EB病毒相关外周T细胞淋巴瘤（EBV-PTCL）是一种单克隆增殖EB病毒感染T细胞的致死性疾病。EBV-PTCL的临床特征包括持续高热、全血细胞减少、肝功能障碍、凝血功能障碍和噬血细胞综合征。EBV- ptcl淋巴瘤细胞在细胞因子产生和细胞毒性方面功能活跃，这可能受到EBV感染的影响。LMP1蛋白是EB病毒最重要的蛋白之一，具有致瘤活性，并有可能上调T细胞中KF-κB活性，是一种有效的细胞因子产生调节剂。因此，阐明LMP1在EBV-PTCL中的作用是很有意义的。本研究对EBV-PTCL患者获得的LMP1基因进行分析，发现EBV-PTCL患者的LMP1基因具有8个氨基酸替换（Q189P、S192T、G212S、S309N、Q322N/H/I、Q334R、L338S、S366T）和10个氨基酸缺失的共同特征。具有这种突变型LMP1的EB病毒可能在EBV-PTCL的发病机制中起作用。此外，在上调NF-κB活性的潜力方面，突变体LMP1具有显著强的活性。因此，可以想象，携带突变体LMP1的EB病毒转化了T细胞，并通过其强烈的NF-κB激活导致EBV-PTCL大量细胞因子的产生。

EB virus associated peripheral T cell lymphoma (EBV-PTCL) is a fatal disorder of monoclonally proliferated EB virus infected T cells. Clinical characteristics of EBV-PTCL consist of persistent high fever, pancytopenia, liver dysfunction, coagulopathy, and hemophagocytic syndrome. Lymphoma cells of EBV-PTCL are functionally active in cytokine production and cytotoxicity, which may be affected by the infected EBV. LMP1 protein, one of the most important proteins of EB virus, has oncogenic activity, and has a potential to up-regulate KF-κB activity, which is a potent cytokine production regulator in T cells. Therefore, it was interesting to elucidate the role of LMP1 in EBV-PTCL.In the present study, we have analyzed LMP1 gene obtained from EBV-PTCL patients, and found that LMP1 from EBV-PTCL shared common features of 8 amino acids replacement (Q189P, S192T, G212S, S309N, Q322N/H/I, Q334R, L338S, S366T) and 10 amino acids deletion. That is EB virus possessing this type of mutant LMP1 may play a role in pathogenesis of EBV-PTCL. Further, as for potential to up-regulation of NF-κB activity, mutant LMP1 has significantly strong activity. Therefore, it is conceivable that EB virus possessing mutant LMP1 transformed T cells, and lead massive cytokine production in EBV-PTCL via its strong NF-κB activation.