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Alterations of the MDV oncogenic regions in an MDV transformed lymphoblastoid cell line

¹ Laboratoire d’Oncologie Virale et Moléculaire, UFR de Biochimie, Université Paris 7-D. Diderot, Paris, France
² INRA Tours, Station de Pathologie Aviaire et Parasitologie, 37380 Nouzilly, France
³ Ecole Nationale Vétérinaire, INRA UR703, 44307 Nantes, Cedex 03, France

Correspondence to:
Professor B Perbal, UFR de Biochimie, Université Paris 7-D. Diderot, 2 Place Jussieu, 75005 Paris, France;
Bernard.Perbal{at}wanadoo.fr

Aims: Lymphoblastoid cell lines derived from Marek’s disease virus (MDV) induced tumours have served as models of MDV latency and transformation. They are stable and can be cultured with no detectable MDV genomic alterations upon repeated passaging. An MDV transformed lymphoblastoid T cell line (T9 cell line) has been reported to contain a disrupted MDV BamHI-H fragment and a Rous associated virus insertional activation of the c-myb protooncogene. In an attempt to define the respective participation of c-myb and MDV in the transformed phenotype of T9 cells, an analysis of MDV oncogenic sequences (BamHI-H, BamHI-A, and EcoQ fragments) was performed in these cells.

Methods: Using two different passages of the T9 cell line (late and early passages), the organisation of the MDV oncogenic regions and their expression in these cells were analysed. In vivo assessment of the oncogenicity of the virus contained within these cells was assessed by injecting them into 1 day old chickens.

Results: In T9 cells maintained in culture for up to six months (late T9), the MDV ICP4 gene was disrupted, whereas the meq gene was actively transcribed. The alterations of the MDV genome in these cells correlated with the inability of the virus to induce the classic signs of Marek’s disease in 1 day old chickens. However, early T9 cells submitted to a limited number of passages induced classic MDV pathogenicity, as efficiently as the MDV control cell line (T5), and did not show gross structural changes in the oncogenic MDV sequences.

Conclusions: Although the expression pattern of the MDV oncogenes in early T9 cells was identical to the one reported for other MDV transformed cells, longterm culture of an MDV transformed cell line containing a RAV insertional activation of the c-myb protooncogene led to the disruption of the MDV BamHI-H and BamHI-A oncogenic regions. In the late T9 cells MEQ was the only detected MDV oncoprotein. These results suggest that in the late T9 cells the truncated MYB protein compensates for the loss of MDV oncoproteins and reinforce the possibility that MEQ and MYB cooperate in the maintenance of the transformed state and the tumorigenic potential of these cells.

Keywords: Marek’s disease virus; meq; pp38; ICP4 homologue gene; c-myb

Abbreviations: CEF, chicken embryo fibroblast; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IR_L, long internal repeat; IR_S, short internal repeat; LATs, latency associated transcripts; MDV, Marek’s disease virus; MHC, major histocompatibility complex; ORF, open reading frame; PBS, phosphate buffered saline; RAV-2, Rous associated virus 2; TAE, Tris acetate EDTA; TR_L, long terminal repeat; TR_S, short terminal repeat; U_S, short unique region; U_L, long unique region

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				T. Okada, M. Takagi, S. Murata, M. Onuma, and K. Ohashi Identification and characterization of a novel spliced form of the meq transcript in lymphoblastoid cell lines derived from Marek's disease tumours J. Gen. Virol., August 1, 2007; 88(8): 2111 - 2120. [Abstract] [Full Text] [PDF]