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.
Epstein-Barr virus (EBV) persists for life in the infected host.Little is known about EBV reactivation and regulation of virus persistence in healthy individuals. We examined tonsils of chronic tonsillitis patients to detect EBV transcripts, EBV genomes and lytic proteins. LMP1 transcripts were observed in 11 of 15 specimens and BZLF1 transcripts were detected in six. Multiple copies of EBV genome equivalents per cell, and ZEBRA-and viral capsid antigen-positive cells were also detected in tonsillar lymphocytes. These results indicate that EBV productively infected cells may survive in the face of immune surveillance in the tonsils. Thus, EBV replication may occur in tonsillar lymphocytes, and tonsillar lymphoid tissues may play a role in the maintenance of EBV load in vivo.
An association between Epstein-Barr virus (EBV) infection and fibroblast proliferation in the interstitial spaces of the lung has been suggested in idiopathic interstitial pneumonia. In this study we show that EBV can infect human lung fibroblasts in vitro. A primary-cultured human lung fibroblast cell line, designated CCD-32Lu, expressed EBV nuclear antigen 1 after coculture with lethally irradiated EBV producing cells. The infection further induced CCD-32Lu cells to produce the fibrogenic cytokines basic fibroblast growth factor (bFGF) and interleukin-1beta. These findings indicate that lung fibroblasts may be a target for EBV infection and suggest that EBV may play a role in increased production of these cytokines and induce fibroblast proliferation in idiopathic interstitial pneumonia.
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