Role of latent membrane protein 1 in chronic active Epstein-Barr virus infection-derived T/NK-cell proliferation

潜伏膜蛋白 1 在慢性活动性 Epstein-Barr 病毒感染引起的 T/NK 细胞增殖中的作用

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作者:Takuto Ito, Hidetaka Kawazu, Takayuki Murata, Seiko Iwata, Saki Arakawa, Yoshitaka Sato, Kiyotaka Kuzushima, Fumi Goshima, Hiroshi Kimura

Abstract

Epstein-Barr virus (EBV) predominantly infects B cells and causes B-cell lymphomas, such as Burkitt lymphoma and Hodgkin lymphoma. However, it also infects other types of cells, including T and natural killer (NK) cells, and causes disorders, such as chronic active EBV infection (CAEBV) and T/NK-cell lymphoma. The CAEBV is a lymphoproliferative disease with poor prognosis, where EBV-positive T or NK cells grow rapidly, although the molecular mechanisms that cause the cell expansion still remain to be elucidated. EBV-encoded latent membrane protein 1 (LMP1) is an oncogene that can transform some cell types, such as B cells and mouse fibroblasts, and thus may stimulate cell proliferation in CAEBV. Here, we examined the effect of LMP1 on EBV-negative cells using the cells conditionally expressing LMP1, and on CAEBV-derived EBV-positive cells by inhibiting the function of LMP1 using a dominant negative form of LMP1. We demonstrated that LMP1 was responsible for the increased cell proliferation in the cell lines derived from CAEBV, while LMP1 did not give any proliferative advantage to the EBV-negative cell line.

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