Interferon Regulatory Factor 7 Is Associated with Epstein-Barr Virus-Transformed Central Nervous System Lymphoma and Has Oncogenic Properties

Authors

Luwen Zhang, University of Nebraska-LincolnFollow
Jun Zhang, University of Nebraska-Lincoln
Que Lambert, Temple University
Channing J. Der, Temple University
Luis Del Valle, Temple University
Judith Miklossy, Temple University
Kamel Kahlili, Temple University
You Zhou, University of Nebraska-LincolnFollow
Joseph S. Pagano, Temple University

Document Type

Article

Date of this Version

12-1-2004

Comments

Published in JOURNAL OF VIROLOGY, Dec. 2004, p. 12987–12995 Vol. 78, No. 23 0022-538X/04/$08.000 DOI: 10.1128/JVI.78.23.12987–12995.2004. Copyright © 2004, American Society for Microbiology. Used by permission.

Abstract

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-immortalized 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.