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Virology. 2010 Sep 30;405(2):464-73. doi: 10.1016/j.virol.2010.06.037. Epub 2010 Jul 15.

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

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1
Division of Infectious Diseases, National Health Research Institutes, Tainan, Taiwan.

Abstract

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.

PMID:
20637487
DOI:
10.1016/j.virol.2010.06.037
[Indexed for MEDLINE]
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