Expression of Epstein–Barr Virus Latent Membrane Protein 1 Protects Jurkat T Cells from Apoptosis Induced by Serum Deprivation

AbstractIt has been generally accepted that inhibition of apoptosis is important in the development of malignancy. To determine whether Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1), the virus-coded transforming oncogene product, has an anti-apoptotic function in non-B-cells, Jurkat T cells were transfected with the LMP1-expression vector pSV2gptMTLM consisting of the human metallothionein promoter and were selected for mycophonolic acid resistance. LMP1-expressing clones of Jurkat cells showed resistance to apoptosis induced by serum deprivation. In LMP1-expressing clones, although the levels of Bcl-2 and Bax were similar to those in the clones of vector transfectants or parental cells, c-Myc expression was significantly depressed. Down-regulation of c-Myc by LMP1 was confirmed by using LMP1-expressing clones treated with CdCl2. Addition of c-mycantisense oligonucleotides to Jurkat cells specifically inhibited apoptosis induced by serum deprivation at the concentrations which suppressed c-Myc expression. These results suggest that LMP1 expression and subsequent down-regulation of c-Myc protect Jurkat T cells from apoptosis induced by serum deprivation. The significance of the anti-apoptotic function of LMP1 in non-B, Jurkat T cells is discussed in relation to the pathogenesis of EBV malignancy