Interferon regulatory factor 4 is involved in Epstein-Barr virus-mediated transformation of human B lymphocytes

Dongsheng Xu, Lingjun Zhao, Luis Del Valle, Judith Miklossy, Luwen Zhang

Research output: Contribution to journalArticle

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Abstract

Epstein-Barr virus (EBV) infection is associated with many human malignancies. In vitro, EBV transforms primary B lymphocytes into continuously growing lymphoblastoid cell lines. EBV latent membrane protein 1 (LMP-1) is required for EBV transformation processes. Interferon regulatory factor 4 (IRF-4) is a transcription factor and has oncogenic potential. We find that high levels of IRF-4 are associated with EBV transformation of human primary B cells in vitro and with EBV type III latency in which LMP-1 is expressed. We show that EBV LMP-1 stimulates IRF-4 expression in B lymphocytes. The stimulation of IRF-4 by LMP-1 requires signaling from LMP-1 and involves cellular NF-κB. The growth of EBV-transformed cells is inhibited when IRF-4 is specifically down-regulated. We further demonstrate that IRF-4 knockdown cells have lower proliferation but higher apoptotic rates than control cells. Finally, IRF-4 is expressed in significant numbers of specimens of primary central nervous system (CNS) lymphomas (12/27 [44.4%]), an EBV-associated malignancy. The association between the expression levels of LMP-1 and IRF-4 is statistically significant (P = 0.011) in these CNS lymphomas. Our data suggest that IRF-4 may be a critical factor in EBV transformation and a useful target in the therapy of EBV-mediated neoplasia.

Original languageEnglish (US)
Pages (from-to)6251-6258
Number of pages8
JournalJournal of virology
Volume82
Issue number13
DOIs
StatePublished - Jul 1 2008

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Human herpesvirus 4
Human Herpesvirus 4
B-lymphocytes
B-Lymphocytes
membrane proteins
Membrane Proteins
Lymphoma
lymphoma
Central Nervous System
central nervous system
Virus Latency
interferon regulatory factor-4
Neoplasms
Epstein-Barr Virus Infections
cells
Transcription Factors
Cell Line
transcription factors
cell lines

ASJC Scopus subject areas

  • Immunology

Cite this

Interferon regulatory factor 4 is involved in Epstein-Barr virus-mediated transformation of human B lymphocytes. / Xu, Dongsheng; Zhao, Lingjun; Del Valle, Luis; Miklossy, Judith; Zhang, Luwen.

In: Journal of virology, Vol. 82, No. 13, 01.07.2008, p. 6251-6258.

Research output: Contribution to journalArticle

Xu, Dongsheng ; Zhao, Lingjun ; Del Valle, Luis ; Miklossy, Judith ; Zhang, Luwen. / Interferon regulatory factor 4 is involved in Epstein-Barr virus-mediated transformation of human B lymphocytes. In: Journal of virology. 2008 ; Vol. 82, No. 13. pp. 6251-6258.
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