Endogenous latent membrane protein 1 in Epstein-Barr virus-infected nasopharyngeal carcinoma cells attracts T lymphocytes through upregulation of multiple chemokines

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-1 alpha, MIP-1 beta and IL-8 contribute to T cell chemotaxis. We further reveal that LMP1-induced production of MIP-1 alpha and MIP-1 beta in NPC cells requires not only two carboxyl-terminal activation regions of LMP1 but also their downstream NF-kappa B 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. (C) 2010 Elsevier Inc. All rights reserved.