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Activation of Epstein–Barr virus by saliva from Sjogren's syndrome patients
Author(s) -
Nagata Yoshifumi,
Inoue Hiroko,
Yamada Koichi,
Higashiyama Hiroyuki,
Mishima Kenji,
Kizu Yasuhiro,
Takeda Ienaka,
Mizuno Fumio,
Hayashi Yoshio,
Saito Ichiro
Publication year - 2004
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.0019-2805.2003.01795.x
Subject(s) - saliva , bzlf1 , mapk/erk pathway , epstein–barr virus , kinase , biology , nfat , protein kinase a , immunology , microbiology and biotechnology , transfection , virus , salivary gland , calcineurin , endocrinology , medicine , gene , herpesviridae , transcription factor , viral disease , biochemistry , transplantation
Summary The aim of this study was to examine the mechanism of Epstein–Barr virus (EBV) activation by soluble factors from the inflamed salivary glands of patients with Sjogren's syndrome (SS). Saliva from SS patients was used to examine the regulation of EBV activation by an inflammatory 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 significant effect on expression of the luciferase gene. A specific 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 β1 (TGF‐β1), 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 inflammatory site may occur in the presence of TGF‐β1 via triggering of the mitogen‐activated protein kinase (MAPK) kinase signalling pathway.