Epstein-Barr virus envelope glycoprotein gp350 induces NF-κB activation and IL-1β synthesis in human monocytes-macrophages involving PKC and PI3-K

Epstein-Barr virus (EBV) is a highly immunotropic human herpesvirus with oncogenic potential and is involved in numerous pathologies, EBV utilizes its major envelope glycoprotein gp350 to bind to its receptor CR2/CD21 on target cells for initiating the infection, We have previously shown that EBV is able to modulate transcription and translation of a number of cytokine genes via its gp350-mediated binding to this receptor. However, the effects of the binding of purified gp350 to CR2/CD21 on plastic-adherent monocyte-macrophages (AMM) have not been investigated, These cells are a rich source of potent proinflammatory and immune-modulating cytokines, and express low levels of CR2/CD21, We show here for the first time that recombinant gp350 (rgp350) causes production of the potent proinflammatory cytokine LG-1 beta in human AMM, Surprisingly, rgp350 is comparable in this capacity to the phorbol ester 12-0-tetradecanoylphorbol 13-acetate, This induction of IL-1 beta production was accompanied by increased steady-state levels of its mRNA in gp350-treated AMM, and was dependent on the specific binding of rgp350 to the EBV receptor CR2/CD21, We also show that the signaling pathways resulting in the induction of IL-1 beta synthesis by rgp350 required protein kinase C and phosphatidylinositol 3,4,5 triphosphate kinase activities and occurred via activation of the NF-kappa B family of transcription factors.