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

Abstract

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.

Identification and characterization of a novel spliced form of the meq transcript in lymphoblastoid cell lines derived from Marek's disease tumours

“…Several studies have shown the presence of multiple forms of the meq transcript (Jones et al, 1992;Le Rouzic et al, 2002). One of these transcripts, termed Meq-sp, was initially identified in the MD cell line, MKT-1 (Peng et al, 1995).…”

“…The meq gene has been known to be polymorphic and several variants have been reported, including L-meq (Chang et al, 2002c). The presence of multiple spliced transcripts of meq has also been suggested in several studies (Jones et al, 1992;Peng & Shirazi, 1996;Le Rouzic et al, 2002). Nevertheless, the functions of Meq and its variants in the establishment of latency or transformation have not been elucidated clearly.…”

Infection and Pathogenesis Mechanisms of Marek's Disease Virus

“…D, dermis; F, feather; FC, follicular cavity (Payne, 2004(Payne, ). al., 1973Handberg et al, 2001;Davidson and Borenshtain, 2003;Baigent et al, 2005 (Beasley et al, 1970;Addinger and Calnek, 1973 Calnek et al, 1984b;Baigent et al, 1998 (Shek et al, 1983;Calnek et al, 1984b (Cantello et al, 1994(Cantello et al, , 1997 (Cantello et al, 1994(Cantello et al, , 1997 (Kung et al, 2001 (Ichijo et al, 1981;Baigent and Davison, 1999;Le Rouzic, 2002 (Baigent et al, 1998;Burgess and Davison, 2002 (Rouse et al, 1973;Payne and Rennie, 1976 Davison, 1999, 2002), 림프세포의 형질 전환 요소인 Meq가 다량 발현된다 (Ross et al, 1997 et al, 1979;Delecluse and Hammerschmidt, 1993a et al, 1979;Delecluse and Hammerschmidit, 1993a;Deleculuse et al, 1993b BamHI-H gene (Cui et al, 1991 (Fynan et al, 1993).…”