The expression and immune modulation of Epstein-Barr virus-encoded oncogene latent membrane protein 1 (N-LMP1) is essential in the pathogenesis of nasopharyngeal carcinoma. In previous studies, cell transformation has been induced by the expression of EBV-encoded N-LMP1 in non-tumour BALB/c-3T3 cells and these cells have then been used to form tumours in T-cell-deficient nude mice. However, studies using this model have been limited by the lack of a competent immune system. To facilitate the study of immune components in N-LMP1-driven oncogenesis, we herein developed a simplified N-LMP1-derived tumour model in immunocompetent mice. Cell transformation was induced by the expression of N-LMP1 in BALB/c-3T3 cells, and these transformants were used to induce oncogenesis in BALB/c mice. In contrast to the 100% successful tumour-induction rate in nude mice treated with monodispersed transformed cells, the tumour incidence in BALB/c mice was only 5-36%. However, the transplantation of tumour fragments into BALB/c mice yielded a reproducible tumour-induction rate of .85%, which is acceptable for most of the research needs. This novel model of N-LMP1-directed oncogenesis in an immunocompetent environment may serve as an important platform for the future assessment of N-LMP1targeted tumour therapies. Keywords Nasopharyngeal carcinoma; Epstein-Barr virus (EBV); oncogene latent membrane protein 1 (N-LMP1); tumour mouse model Nasopharyngeal carcinoma (NPC) is a retronasal malignant tumour consistently associated with the latent state of Epstein-Barr virus (EBV) infection. The expression of EBV-encoded oncogene latent membrane protein 1 (LMP1) is considered as a determining factor for the processes of cell immortalization and malignant transformation (Wang et al. 1985, Baichwal & Sugden 1988, Raab-Traub 2002. LMP1, a member of the tumour necrosis factor receptor family, possesses the unique property of exerting both oncogenicity and immune-modulatory functions by ligand-independent activation of multiple intracellular signalling pathways and downstream genes (Gires et al. 1997, Li & Chang 2003. Protein sequence analysis has identified two major types of LMP1: prototype LMP1, originally identified in EBV-positive B lymphoma (B95-8) cells (B-LMP1) (Kaye et al. 1993); and N-LMP1, a variant with multiple

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In this study, we investigated the functional outcomes of CD4

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