Analysis of immortalization of normal T lymphocytes by Epstein-Barr virus

EB病毒对正常T淋巴细胞的永生化分析

• 批准号: 08670332
• 负责人: IMAI Shosuke
• 金额: $ 1.41万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670332/
• 关键词: Epstein-Barr virus; Tlymphocytes; immortalization; recombinant virus

This study aimed to investigate the unclarified Epstein-Barr virus (EBV) activity on normal T-lymphocyte immortalization. For infection experiments, we used recombinant EBV (Akata strain) carrying the neomycin-resistance gene (neo-EBV). Although normal peripheral T lymphocytes could not be infected by neo-EBV,primary thymocytes revealed EBNA1 expression after virus exposure. However, the following selection culture did not yield permanently growing thymocytes infected with neo-EBV even in the presence of interleukin 2 (IL-2) in culture medium, probably because virus-infected thymocytes tended to enter into the virus lytic cycle. These results suggest that EBV infection of thymocytes results in the permissive, not latent, infection in vivo, which may be associated with EBV-induced T-lymphoproliferative disorders.We are currently studying whether EBNA2, or-3A,or-3C gene can alter EBV-infected T-cell lines, the growth of which is dependent on IL-2 so far, such as in terms of aquisition of IL-2 independency or more malignant phenotype.

本研究旨在探讨eb病毒（EBV）对正常t淋巴细胞永生化的影响。感染实验采用携带新霉素耐药基因（neo-EBV）的重组EBV （Akata株）。虽然正常外周血T淋巴细胞不能被新ebv感染，但原代胸腺细胞在病毒暴露后出现EBNA1表达。然而，即使在培养基中存在白细胞介素2 (IL-2)，以下选择培养也不能产生永久生长的感染新ebv的胸腺细胞，这可能是因为病毒感染的胸腺细胞倾向于进入病毒裂解周期。这些结果表明，eb病毒感染胸腺细胞导致体内许可性感染，而不是潜伏性感染，这可能与eb病毒诱导的t淋巴增生性疾病有关。我们目前正在研究EBNA2、or- 3a、or- 3c基因是否可以改变ebv感染的t细胞系，这些细胞的生长迄今依赖于IL-2，例如在获得IL-2独立性或更恶性的表型方面。

项目成果

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Yoshiyama,H：“不同于 CD21 的新病毒受体的存在的意义。”

Harabuchi, Y., Imai, S., Wakashima, J., Hirao, M., Kataura, A., Osato, T., Kon, S.: "Nasal T-cell lymphoma causally associated with Epstein-Barr virus. clinicopathologic, phenotypic, and genotypic studies." Cancer. 77. 2137-2149 (1996)

Harabuchi, Y.、Imai, S.、Wakashima, J.、Hirao, M.、Kataura, A.、Osato, T.、Kon, S.：“鼻 T 细胞淋巴瘤与 Epstein-Barr 病毒有因果关系。临床病理学

Azuma, H., Sakata, Y., Sasaki, K., Oka, T., Hironaka, T., Hirai, K., Imai, S., Osato, T., Okuno, A.: "Hodgkin's disease developed in a patient with extremely high serum antibody titers against Epstein-Barr virus associated antigens without chronic illness

Azuma, H.、Sakata, Y.、Sasaki, K.、Oka, T.、Hironaka, T.、Hirai, K.、Imai, S.、Osato, T.、Okuno, A.：“霍奇金病发展于

Harabuchi,Y.: "Nasal T-cell lymphoma causally associated with Epstein-Barr virus." Gann Monograph on Cancer Res.45. 129-137 (1998)

Harabuchi,Y.：“鼻 T 细胞淋巴瘤与 Epstein-Barr 病毒有因果关系。”