title: Epstein Barr virus inhibits the stimulatory effect of TLR7/8 and TLR9 agonists but not CD40 ligand in human B lymphocytes.
abstract: Viruses and other microorganisms express specific pathogen-associated molecular patterns that are recognized by cell surface or endosome-associated Toll-like receptors (TLR). There are many examples of viruses that have developed strategies to modulate TLR signaling through the use of viral or cellular molecules. Epstein-Barr virus (EBV) has recently been found to display a complex interaction with TLR. The aim of this study was to asses the effect of EBV infection on proliferative capacity of TLR7/8 and 9 agonist and CD40 ligand (CD40L) in normal B lymphocytes. Our results demonstrate that EBV induces a significant inhibition in proliferative response to TLR7/8 (P < 0.004) and TLR9 (P < 0.000) agonists but not to CD40L stimulation in enriched human normal B lymphocytes. Similar inhibitory effect was also observed in B lymphocytes prestimulated with the TLR agonists, implying that the suppressive effect is not due to downregulation of TLR protein expression by EBV. EBV infection did not induce apoptosis and did not downregulate TLR7/8 mRNA expression in B lymphocytes. Our results suggest that EBV might be able to evade the immune system by modulation of the TLR signaling pathway.
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran 14155-6559, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Younesi
authors.forename: Haleh
authors.initials: H
authors.lastname: Nikzamir
authors.forename: Mehdi
authors.initials: M
authors.lastname: Yousefi
authors.forename: Jalal
authors.initials: J
authors.lastname: Khoshnoodi
authors.forename: Mohammd
authors.initials: M
authors.lastname: Arjmand
authors.forename: Hodjatallah
authors.initials: H
authors.lastname: Rabbani
authors.forename: Fazel
authors.initials: F
authors.lastname: Shokri
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D023201:CD40 Ligand / Q000502:physiology*; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000502:physiology; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D051200:Toll-Like Receptor 8 / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000502:physiology*
chemical_list: D016328:NF-kappa B; C495348:TLR7 protein, human; C495349:TLR8 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D023201:CD40 Ligand