Division of Infectious Diseases, National Health Research Institutes, Tainan, Taiwan.
Virology. 2010 Sep 30;405(2):464-73. doi: 10.1016/j.virol.2010.06.037. Epub 2010 Jul 15.
Tumor-infiltrating T lymphocytes are considered to facilitate development of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), but how EBV in NPC tumor cells directs T cell infiltration remains unclear. Here we compare EBV-infected NPC cells with and without spontaneous expression of viral latent membrane protein 1 (LMP1) and find that culture supernatants of LMP1-positive NPC cells exert enhanced chemoattraction to primary T cells. Knockdown of endogenous LMP1 in the cells suppresses the chemotactic activity. Endogenous LMP1 in NPC cells upregulates multiple chemokines, among which MIP-1alpha, MIP-1beta and IL-8 contribute to T cell chemotaxis. We further reveal that LMP1-induced production of MIP-1alpha and MIP-1beta in NPC cells requires not only two carboxyl-terminal activation regions of LMP1 but also their downstream NF-kappaB and JNK pathways. This study corroborates that endogenous LMP1 in EBV-infected NPC cells induces multiple chemokines to promote T cell recruitment and perhaps other pathogenic events in NPC.
肿瘤浸润 T 淋巴细胞被认为有助于 Epstein-Barr 病毒（EBV）相关的鼻咽癌（NPC）的发展，但 NPC 肿瘤细胞中的 EBV 如何指导 T 细胞浸润仍不清楚。在这里，我们比较了自发表达病毒潜伏膜蛋白 1（LMP1）和不表达 LMP1 的 EBV 感染 NPC 细胞，发现 LMP1 阳性 NPC 细胞的培养上清液对原代 T 细胞具有更强的趋化作用。细胞内源性 LMP1 的敲低抑制了趋化活性。NPC 细胞中的内源性 LMP1 上调了多种趋化因子，其中 MIP-1alpha、MIP-1beta 和 IL-8 有助于 T 细胞趋化。我们进一步揭示，LMP1 诱导 NPC 细胞中 MIP-1alpha 和 MIP-1beta 的产生不仅需要 LMP1 的两个羧基末端激活区，还需要其下游的 NF-kappaB 和 JNK 途径。这项研究证实，EBV 感染的 NPC 细胞中的内源性 LMP1 诱导多种趋化因子来促进 T 细胞募集，并可能促进 NPC 中的其他致病事件。
