Epstein-Barr virus envelope glycoprotein gp350 induces NF-kappaB activation and IL-1beta 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 IL-1beta in human AMM. Surprisingly, rgp350 is comparable in this capacity to the phorbol ester 12-0-tetradecanoylphorbol 13-acetate. This induction of IL-1beta 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-1beta synthesis by rgp350 required protein kinase C and phosphatidylinositol 3,4,5 triphosphate kinase activities and occurred via activation of the NF-kappaB family of transcription factors.-D'Addario, M., Ahmad, A., Xu, J. W., Menezes, J. Epstein-Barr virus envelope glycoprotein gp350 induces NF-kappaB activation and IL-1beta synthesis in human monocytes-macrophages involving PKC and PI3-K.
D'Addario
M
M
Laboratory of Immunovirology, Department of Microbiology and Immunology, and Pediatric Research Center, University of Montreal, Quebec, Canada.
Ahmad
A
A
Xu
J W
JW
Menezes
J
J
D000911:Antibodies, Monoclonal; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism* / Q000821:virology; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism* / Q000821:virology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D017464:Receptors, Complement 3d / Q000276:immunology; D015398:Signal Transduction; D014763:Viral Matrix Proteins / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D017464:Receptors, Complement 3d; D014763:Viral Matrix Proteins; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C