EBERs the Small Viral Non-coding RNAs are Tumourigenic and Disturb the Interferon Response in Vivo

Tsimbouri, P. , Chiou, Y.-C. and Wilson, J.B. (2008) EBERs the Small Viral Non-coding RNAs are Tumourigenic and Disturb the Interferon Response in Vivo. Beatson International Cancer Conference Cell Growth and Metabolism, Glasgow, UK, 15-18 Jun 2008.

Abstract

Non-coding RNAs produced by viruses have been determined to have critical functions in infected cells, particularly in gene regulation. EBER1is a non-coding, polymerase III transcribed RNA expressed by Epstein-Barr Virus (EBV) in most EBV associated tumour cells and has been demonstrated to contribute to the maintenance of the malignant phenotype of Burkitt’s lymphoma cells (Komano et al., 1999). Nanbo et al. (2002) that expression of EBER1 in EBV-negative cells could protect the cell from interferon (IFN)-induced apoptosis. These results have suggested that EBER1 plays a role in tumourigenesis. However, to date the mechanism by which EBER1 achieves this is unclear. In the present study, the action of EBER1 in vivo in transgenic mice is under investigation. EBER1 is expressed in lymphoid tissues in these mice, which show a phenotype of lymphoid expansion at a young age as well as the development of B-cell lymphoma in later life. In order to explore the interferon response to double stranded RNA in these mice, they were injected with the dsRNA analogue polyriboinosinic-polyribocytylic acid (pI:C). While pIC induces serum IFNα levels in wild type mice we have found that this induction is significantly higher in EBER1 mice for IFNα, ß and γ. Furthermore, the Jak-STAT signalling pathway is activated to a greater extent in the transgenic mice compared to wild type. These results suggest that EBER1 promotes the interferon response, contrary to current speculations concerning the mechanism of action of EBER1. How this activity can be reconciled with a function in the viral life cycle is indeed puzzling and subject for further study In order to test whether EBER1 affects the adaptive immune response through its modulation of the innate immune responses, transgenic anc control mice were antigenically challenged and their antigen specific response was examined (data will be presented). Furhter analysis of the downstream events may shed light on how EBER1 contributes to tumourigenesis.

• Item Type: Conference or Workshop Item
• Status: Published
• Refereed: No
• Glasgow Author(s) Enlighten ID: Wilson, Professor Joanna and Tsimbouri, Dr Monica
• Authors: Tsimbouri, P., Chiou, Y.-C., and Wilson, J.B.
• Subjects: Q Science > QR Microbiology > QR355 Virology
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences; College of Medical Veterinary and Life Sciences > School of Life Sciences