CD40 ligand is a critical effector of Epstein-Barr virus in host cell survival and transformation
CD40 ligand is a critical effector of Epstein-Barr virus in host cell survival and transformation
复制标题
DOI：
10.1073/pnas.1231363100
复制
发表时间：
2003-06-24
影响因子：
11.1
通讯作者：
Yamanashi, Y
中科院分区：
文献类型：
--
作者：
Imadome, KI;Shirakata, M;Yamanashi, Y
EB 病毒 (EBV) 与多种人类疾病有关，包括淋巴恶性肿瘤，它持续感染外周 B 细胞并将其转化为类淋巴母细胞系。在这里，我们发现 EBV 同样感染 X 连锁高 IgM 综合征患者和健康捐献者的 B 细胞；然而，由于患者的CD40配体（CD40L）基因功能失调，它很难转化X连锁高IgM综合征B细胞。与 CD40 不同，CD40L 通常不在 B 细胞上表达。然而，我们发现正常 B 细胞的 EBV 感染诱导 CD40L 表达，作为宿主细胞转化和存活的关键效应子。此外，与 T 细胞恶性肿瘤有关的外周 T 细胞的慢性活动性 EBV 感染与 CD40 的异位表达相关，并且在 Jurkat T 细胞中，EBV 感染诱导 CD40 表达。这些结果表明，EBV 感染诱导宿主细胞中的 CD40L/CD40 信号传导，这似乎在其持续感染和淋巴细胞恶性肿瘤中发挥重要作用。
Epstein-Barr virus (EBV), implicated in numerous human diseases, including lymphoid malignancies, persistently infects peripheral B cells and transforms them into lymphoblastoid cell lines. Here we found that EBV equally infected B cells from patients with X-linked hyper IgM syndrome and those from healthy donors; however, it hardly transformed X-linked hyper IgM syndrome B cells, because of the dysfunctional gene of CD40 ligand (CD40L) of the patients. Unlike CD40, CD40L is not usually expressed on B cells. However, we found that EBV infection of normal B cells induced CD40L expression as a critical effector in host cell transformation and survival. Moreover, chronic active EBV infection of peripheral T cells, implicated in T cell malignancies, was associated with ectopic expression of CD40, and, in Jurkat T cells, EBV infection induced CD40 expression. These results suggest that EBV infection induces CD40L/CD40 signaling in host cells, which appears to play an essential role in its persistent infection and malignancies of lymphocytes.