Transactivation of the CCL5/RANTES gene by Epstein-Barr virus latent membrane protein 1

Jun Nosuke Uchihara, Alan M. Krensky, Takehiro Matsuda, Hirochika Kawakami, Taeko Okudaira, Masato Masuda, Takao Ohta, Nobuyuki Takasu, Naoki Mori*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Chemokines and chemokine receptors mediate lymphocyte migration and tissue localization. To analyze CCL5 (RANTES) expression by EBV-infected cells, we examined the expression of CCL5 in BL cell lines. Among 4 BL cell lines, those infected with EBV selectively expressed the CCL5 gene and secreted CCL5. Four cell lines also expressed CCR5, a receptor for CCL5. EBV-encoded LMP-1, a pleiotropic protein that effects gene expression, cell transformation, growth and death, induces expression of CCL5 mRNA and secretion of CCL5 in the EBV-negative BL cell line BJAB and the embryonic kidney cell line 293T. HDACI-stimulated endogenous LMP-1 also induced CCL5 expression in an EBV-positive BL cell line. Analysis of the CCL5 promoter revealed that it is activated by both LMP-1 C-terminal activation domains, CTAR-1 and CTAR-2, which can activate NF-κB signaling. Coexpression of IκBα, IκBβ, IKKα, IKKβ, NIK and TRAF2 dominant-negative constructs, with LMP-1 inhibited the activation of the CCL5 promoter by LMP-1, suggesting that LMP-1 induces CCL5 via NF-κB signaling. The NF-κB binding sites, R(A/B), located at positions -71 to -43 relative to the putative transcription start site in the CCL5 promoter, were essential for the activation of CCL5 gene expression by LMP-1. These results indicate that the activation of the NF-κB pathway by LMP-1 is required for the activation of CCL5 expression.

Original languageEnglish (US)
Pages (from-to)747-755
Number of pages9
JournalInternational Journal of Cancer
Volume114
Issue number5
DOIs
StatePublished - May 1 2005

Keywords

  • Burkitt's lymphoma
  • CCL5
  • Epstein-Barr virus
  • LMP-1
  • NF-κK

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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