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

EB病毒在EB病毒相关外周T细胞淋巴瘤中的细胞生物学分析

基本信息

批准号：
11670778
负责人：
MORIMOTO Akira
金额：
$ 2.3万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670778/
关键词：
EBV associated peripheral T cell lymphoma EBV LMP1 Cytokine EBV EBV関連末梢T細胞性悪性リンパ腫 LMP-1 NFκ-B 関連末梢T細胞性悪性リンパ腫 LMP1遺伝子 B95.8 30bp deletion

项目摘要

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.

EB病毒相关性外周T细胞淋巴瘤(EBV-PTCL)是一种由EB病毒感染的T细胞单克隆性增殖所致的致死性疾病。EBV-PTCL的临床特征包括持续高热、全血细胞减少、肝功能障碍、凝血障碍和吞噬血细胞综合征。EBV-PTCL的淋巴瘤细胞在细胞因子的产生和细胞毒作用方面具有功能活性，这可能受感染的EBV的影响。LMP1蛋白是EB病毒最重要的蛋白之一，具有致癌活性，并有可能上调KF-κB的活性，而KF-LMP1 B是T细胞中一种强大的细胞因子产生调节因子。本研究对EBV-PTCL患者的LMP1基因进行了分析，发现EBV-PTCL的LMP1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。也就是说，携带该突变LMP1的EB病毒可能在EBV-PTCL的发病机制中起一定作用。此外，对于上调NF-κB活性的可能性，突变体LMP1具有明显的较强活性。因此，可想而知，具有突变型LMP1基因的EB病毒可以转化T细胞，并通过其强大的NF-κB活性导致EB病毒-PTCL中大量细胞因子的产生。