COMPARISON OF THE RESPONSE TO T-CELL ACTIVATION BY INTEGRATED HIV-1 AND HTLV-1 LTR-LACZ VECTORS

Human Jurkat T-cell clones containing stably integrated HIV-1 LTR or H TLV-1 LTR/lacZ Vectors were studied to compare the responses of integr ated LTRs to T-cell activation. Responses were compared also with thos e obtained in parallel with Jurkat cells stably expressing lacZ under the control of the cellular enhancer element NF-AT of the IL-2 promote r. Activation induced via the cell surface TCR/CD3 complex or the CD28 receptor elicited responses from the LTR of HIV-1; however, HTLV-1 LT R-directed expression was not observed following triggering of these c ell surface pathways. Mitogenic activation by elevation of intracellul ar calcium (Ca2+) levels along with protein kinase C (PKC) signals was required for optimal expression of the HIV-1 LTR and the NF-AT elemen t; however, increased intracellular Ca2+ was inhibitory to PKC-mediate d expression from the HTLV-1 LTR. Time course experiments revealed a s ustained PKC-mediated response by the HTLV-1 LTR, which was detectable in the absence of Ca2+ as early as 6 hr following stimulation. In con trast to the HTLV-1 LTR, in time course experiments the HIV-1 LTR resp onded to stimulation by mitogenic activation of PKC in the absence and presence of Ca2+ and by antiCD3 with lacZ expression beginning as ear ly as 3 hr poststimulation. These results suggest that the HTLV-1 LTR appears to be refractory to several cellular pathways which are upregu latory to the HIV-1 LTR. (C) 1995 Academic Press, Inc.