title: Interferon regulatory factor 7 is associated with Epstein-Barr virus-transformed central nervous system lymphoma and has oncogenic properties.
abstract: 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-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.
authors.affiliation: NE Center for Virology, School of Biological Sciences, University of Nebraska, 1901 Vine St., Lincoln, NE 68588, USA. lzhang2@unlnotes.unl.edu
authors.forename: Luwen
authors.initials: L
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Que
authors.initials: Q
authors.lastname: Lambert
authors.forename: Channing J
authors.initials: CJ
authors.lastname: Der
authors.forename: Luis
authors.initials: L
authors.lastname: Del Valle
authors.forename: Judith
authors.initials: J
authors.lastname: Miklossy
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Pagano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001932:Brain Neoplasms / Q000821:virology*; D002455:Cell Division; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D050839:Interferon Regulatory Factor-7; D008223:Lymphoma / Q000821:virology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D041681:NIH 3T3 Cells; D014763:Viral Matrix Proteins / Q000032:analysis
chemical_list: D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; C494235:Irf7 protein, mouse; D014763:Viral Matrix Proteins