Activation of Epstein–Barr virus by saliva from Sjogren's syndrome patients

Abstract

SUMMARYThe aim of this study was to examine the mechanism of Epstein±Barr virus (EBV) activation by soluble factors from the in¯amed salivary glands of patients with Sjogren's syndrome (SS). Saliva from SS patients was used to examine the regulation of EBV activation by an in¯amma-tory salivary microenvironment. Transient transfection of the EBV-negative salivary gland cell line (HSY) with BZLF1, a trans-activating EBV gene promoter-fusion construct (Zp-luc), was used in this study. The results showed that under conditions where the BZLF1 promoter is activated by potent stimuli, SS saliva (from eight of 12 patients) exerts a signi®cant effect on expression of the luciferase gene. A speci®c inhibitor of protein kinase C did not affect the SS saliva-induced Zp-luc activity, whereas treatment with inhibitors of calmodulin, calcineurin and IP 3 , dose-dependently decreased this induction. Transforming growth factor b1 (TGF-b1), which is known to be expressed in SS salivary glands, dose-dependently induced Zp-luc activity. Hence, these results demonstrate the activation of EBV by SS saliva and suggest that EBV activation at the in¯ammatory site may occur in the presence of TGF-b1 via triggering of the mitogen-activated protein kinase (MAPK) kinase signalling pathway.

Aryl Hydrocarbon Receptor-Mediated Induction of EBV Reactivation as a Risk Factor for Sjögren’s Syndrome

“…3, 4). Our previous study demonstrated that Zp221 activity and BZLF1 transcription were induced by saliva from SS patients (63). TGFb1, which is expressed in SS salivary glands, induced Zp221 activity via the MAPK signaling pathway.…”

Immune regulation and B-cell depletion therapy in patients with primary Sjögren’s syndrome

“…Involvement of virus has been speculated for a long time, but despite the fact that several candidate viruses have been thought to play a role (e.g. EpsteineBarr virus [20,21] and coxsackieviruses [22]), evidence for their contribution in the initiation of the disease is still lacking.…”

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“…Therefore viral latency or intensive reactivation may have effects on the antibody production of B lymphocytes, and a contribution of EBV to various autoimmune diseases has been suggested (2,4,5,9,14,(17)(18)(19)(20)22,25,(30)(31)(32)34). For example, in multiple sclerosis (MS), and systemic lupus erythematosus (SLE), EBV infection is thought to be an important environmental trigger (4,22,34).…”