A HUMAN T-LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) LONG TERMINAL REPEAT-DIRECTED ANTISENSE C-MYC CONSTRUCT WITH AN EPSTEIN-BARR-VIRUS REPLICON VECTOR INHIBITS CELL-GROWTH IN A HTLV-I-TRANSFORMED HUMAN T-CELL LINE

A panel of EB virus replicon-based vectors was constructed to examine the relative utility of four distinct eukaryotic promoters for high-level gene expression in a HTLV-1-transformed human T cell line, HUT102. We found that HTLV-I LTR, which is trans-activated by the viral tax protein, was most suited for EBV vector-based stable gene expression in it. We prepared a HTLV-I LTR-directed antisense c-myc construct with an EBV vector. This antisense plasmid suppressed c-myc expression and inhibited growth of HUT102 cells in vitro with unaltered expression of tax. Non-specific plasmid toxicity was excluded by showing that the antisense construct had little effect on growth and c-myc expression of HTLV-I-negative Jurkat T cells, in which the viral LTR is expected to be less active. Our results indicate that c-myc may play an important role in the deregulated growth of HTLV-I-transformed T cells.