Activation of Epstien-Barr virus by saliva from Sjogren’s syndrome patients

Speaker : 蕭冠中                                         Time : 3/31/03

Commentator : 呂政展 老師                               Place : 601

Abstract:

      Sjogren’s syndrome (SS) is an organ-specific autoimmune disease caused by the progressive loss of exocrine glands and is associated with several autoimmune phenomena. Although the pathogenesis of SS remained unclear, high incidence of EBV reactivation was suggested to contribute to the immune response in target organs.¹ After primary infection, replication of viral genes and transcriptional induction of immediate-early genes mediated by expression of the BZLF1 gene was required for EBV reactivation.² However, how viral reactivation of EBV is induced in lesions associated with SS, and which signaling pathway are involved in the process of viral reactivation, have not yet been clarified. In order to elucidate the mechanism underlying the EBV reactivation involved in the pathogenesis and progression of SS, transient transfection of the EBV-negative salivary gland cell line (HSY) with BZLF1 promoter fusion construct (Zp-luc) was used in this study. Their results showed that the BZLF1 promoter is activated by SS saliva which exert a significant affect on expression of the luciferase activity. The PKC inhibitor does not affect luciferase activity, but the inhibitors of IP3, calmodulin and calcineurin decrease Zp-luc activity. TGF-b1, which is known to be expressed in SS, can further enhance Zp-luc activity. Therefore, these results demonstrated the EBV reactivation model in SS and found that expression of the BZLF1 gene in glandular epithelial cells might be induced in the presence of TGF-b1 via MAPK and calcium/calmodulin dependent pathways.

1.       Mariette, X., Gozlan, J., Clerc, D., Bisson, M. & Morinet, F. Detection of Epstein-Barr virus DNA by in situ hybridization and polymerase chain reaction in salivary gland biopsy specimens from patients with Sjogren's syndrome. Am J Med 90, 286-94 (1991).

2.       Rooney, C. M., Rowe, D. T., Ragot, T. & Farrell, P. J. The spliced BZLF1 gene of Epstein-Barr virus (EBV) transactivates an early EBV promoter and induces the virus productive cycle. J Virol 63, 3109-16 (1989).