TAX-INDEPENDENT STIMULATION OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I EXPRESSION AND DIFFERENTIAL-EFFECTS ON ITS INFECTIVITY BY SUBTOXIC AND TOXIC DOSES OF 3-METHYLCHOLANTHRENE

Using the human T-cell leukemia virus type I(HTLV-I) infected SLB-I T- cell line, we showed in this study that 5-d treatment with the maximal subtoxic 3-methylcholanthrene (3-MC) dose (0.25 mu g/ml), as well as with a 3-MC dose that inhibits 50% of the cell growth (5 mu g/ml), pro foundly increased the level of viral RNA. Exposure to these 3-MC doses for 5 d before transient transfection of HTLV-I LTR-CAT construct int o these cells markedly stimulated CAT activity, indicating that 3-MC e xerted its effect by a trans-acting mechanism. A similar stimulation w as observed when this construct was transfected into 3-MC treated unin fected Jurkat cells, indicating that this trans-acting effect was inde pendent of the viral tax protein. However, although the subtoxic 3-MC dose increased also the capacity of SLB-I cells to transmit the virus to normal peripheral blood lymphocytes in coculture, the toxic dose st rongly reduced this capacity. No inhibition by this toxic dose was obs erved in the viral protein synthesis or processing nor in the final re lease of the virus from the cells. However, the virions released under the influence of this 3-MC dose were found to contain mainly the uncl eaved gag precursor polypeptide and a low level of reverse transcripta se. Thus, the reduced virus transmission capacity of the host cells ca n be ascribed to this structural defect, which presumably lowered the viral infectivity.