Endogenous latent membrane protein 1 in Epstein–Barr virus-infected nasopharyngeal carcinoma cells attracts T lymphocytes through upregulation of multiple chemokines
2010; Elsevier BV; Volume: 405; Issue: 2 Linguagem: Inglês
10.1016/j.virol.2010.06.037
ISSN1096-0341
AutoresHsiao-Ching Lai, Jenn-Ren Hsiao, Chaio-Wei Chen, Shih-Yi Wu, Chien-Hsun Lee, Ih‐Jen Su, Kenzo Takada, Yao Chang,
Tópico(s)Histiocytic Disorders and Treatments
ResumoTumor-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-1α, MIP-1β and IL-8 contribute to T cell chemotaxis. We further reveal that LMP1-induced production of MIP-1α and MIP-1β in NPC cells requires not only two carboxyl-terminal activation regions of LMP1 but also their downstream NF-κB 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.
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