Imperial College London is one of the leading Universities in the United Kingdom and has an outstanding research reputation in infectious diseases, one of the main research themes within its Faculty of Medicine. The Departments of Immunology and Virology are part of the Wright-Fleming Institute in the Faculty of Medicine, which has experts in many aspects of infectious diseases and immunology research. The Departments occupy refurbished and well equipped laboratories with excellent research facilities.

Two small RNAs (EBER1 and 2) are abundantly expressed from the EBV genome in EBV associated cancers but the function of these EBER RNAs remains unclear. The purpose of this project is to identify the molecular mechanisms of EBER RNA function, taking advantage of novel expression systems we have developed for the EBER RNAs and our preliminary identification of target genes whose expression is modulated by EBER RNAs. This will lead to assays for specifically inhibitors of EBER function, giving novel therapeutic approaches to EBV asociated cancer. The human T-lymphotropic virus type 1 (HTLV-1) causes two distinct types of disease: the aggressive T-cell leukaemia/lymphoma and a number of chronic inflammatory conditions, notably HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In 95% of HTLV-1-infected individuals the virus persists indefinitely without causing disease. Neither the pathogenesis of these diseases nor the mechanism of persistent infection of HTLV-1 has been well understood. The aim of our work in INCA is to test two hypotheses: That histone deacetylase inhibitors can increase HTLV-1 gene expression in HTLV-1-infected cells (including ATL cells) and thereby increase the exposure of leukaemic cells to CTL surveillance; second, that CTLs determine the leukaemia cell burden (cell count) in chronic cases of ATL.

Amon W, Binné UK, Bryant H, Jenkins PJ, Elgueta Karstegl C and Farrell PJ. Lytic cycle gene expression of Epstein-Barr virus. Journal of Virology 78: 13460-13469, 2004. Spender L, Whiteman H, Elgueta Karstegl C, and Farrell PJ. Transcriptional cross-regulation of RUNX1 by RUNX3 in human B cells. Oncogene 24: 1873-1881, 2005. Spender LC, Lucchesi W, Bodelon G, Bilancio A, Elgueta Karstegl C, Asano T, Dittrich-Breiholz O, Kracht M, Vanhaesebroeck B and Farrell PJ. Cell target genes of Epstein-Barr virus transcription factor EBNA-2: induction of the p55-Alpha regulatory subunit of PI3-kinase and role in survival of EREB2.5 cells. J. Gen Virol. 87: 2859 - 2867, 2006. Igakura, T., J. C. Stinchcombe, P. K. C. Goon, G. P. Taylor, J. N. Weber, G. M. Griffiths, Y. Tanaka, M. Osame, and C. R. M. Bangham. 2003. Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton. Science 299, 1713-1716. Bangham, C. R. M. and M. Osame. 2005. The cellular immune response to HTLV-1. Oncogene 24, 6035–6046. Mosley A. J., Meekings K. N., McCarthy C., Shepherd D., Cerundolo V., Mazitschek R., Tanaka Y., Taylor G. P., Bangham C. R. 2006. Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell anti-viral function in HTLV-I infection. Blood, 108, 3801-7.