Interferon regulatory factor 7 is associated with Epstein-Barr virus-transformed central nervous system lymphoma and has oncogenic properties

Luwen Zhang, Jun Zhang, Que Lambert, Channing J. Der, Luis Del Valle, Judith Miklossy, Kamel Khalili, You Zhou, Joseph S. Pagano

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48 Scopus citations


Interferon regulatory factor 7 (IRF-7) is implicated in the regulation of Epstein-Barr virus (EBV) latency. EBV transforms primary B cells, and the major EBV oncoprotein, latent membrane protein 1 (LMP-1), is required for the process. LMP-1 both induces the expression of IRF-7 and activates the IRF-7 protein by phosphorylation and nuclear translocation. Here we report that the expression of IRF-7 is increased in EBV-imraortalized B lymphocytes compared with that in primary B cells. IRF-7 was phosphorylated and predominantly localized in the nucleus in the immortalized cells. The expression of IRF-7 was detected in 19 of 27 specimens of primary lymphomas of the human central nervous system by immunohistochemical analysis. The association between LMP-1 and IRF-7 was statistically highly significant for these specimens. An appreciable amount of the IRF-7 expressed in lymphoma cells was localized in the nucleus. Furthermore, IRF-7 promoted the anchorage-independent growth of NIH 3T3 cells. LMP-1 and IRF-7 showed additive effects on the growth transformation of NIH 3T3 cells. IRF-7-expressing NIH 3T3 cells formed tumors in athymic mice. Thus, IRF-7 has oncogenic properties and, along with LMP-1, may mediate or potentiate the EBV transformation process in the pathogenesis of EBV-associated lymphomas.

Original languageEnglish (US)
Pages (from-to)12987-12995
Number of pages9
JournalJournal of virology
Issue number23
StatePublished - Dec 1 2004


ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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