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‐macro‐phages (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 IL‐1 β in human AMM. Surprisingly, rgp350 is comparable in this capacity to the phorbol ester 12–0‐tetradecanoylphorbol 13‐acetate. This induction of IL‐1 β 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 β synthesis by rgp350 required protein kinase C and phosphatidylinositol 3,4,5 triphosphate kinase activities and occurred via activation of the NF‐κB family of transcription factors.—D’Addario, M., Ahmad, A., Xu, J. W., Menezes, J. Epstein‐Barr virus envelope glycoprotein gp350 induces NF‐κB activation and IL‐1 β synthesis in human monocytes‐macrophages involving PKC and PI3‐K. FASEB J. 13, 2203–2213 (1999)