Comparison of the Response to T-cell Activation by Integrated HIV-1 and HTLV-1 LTR-lacZ Vectors

Abstract

Human Jurkat T-cell clones containing stably integrated HIV-1 LTR or HTLV-1 LTR/lacZ vectors were studied to compare the responses of integrated LTRs to T-cell activation. Responses were compared also with those obtained in parallel with Jurkat cells stably expressing lacZ under the control of the cellular enhancer element NF-AT of the IL-2 promoter. Activation induced via the cell surface TCR/CD3 complex or the CD28 receptor elicited responses from the LTR of HIV-1; however, HTLV-1 LTR-directed expression was not observed following triggering of these cell surface pathways. Mitogenic activation by elevation of intracellular calcium (Ca2+) levels along with protein kinase C (PKC) signals was required for optimal expression of the HIV-1 LTR and the NF-AT element; however, increased intracellular Ca2+ was inhibitory to PKC-mediated expression from the HTLV-1 LTR. Time course experiments revealed a sustained PKC-mediated response by the HTLV-1 LTR, which was detectable in the absence of Ca2+ as early as 6 hr following stimulation. In contrast to the HTLV-1 LTR, in time course experiments the HIV-1 LTR responded to stimulation by mitogenic activation of PKC in the absence and presence of Ca2+ and by antiCD3 with lacZ expression beginning as early as 3 hr poststimulation. These results suggest that the HTLV-1 LTR appears to be refractory to several cellular pathways which are upregulatory to the HIV-1 LTR.

T-Cell Receptor/CD28 Engagement When Combined with Prostaglandin E2Treatment Leads to Potent Activation of Human T-Cell Leukemia Virus Type 1

“…Although we have not yet fully addressed this issue, the absence of possible negative regulatory elements or the spatial reorganization of the TRE repeats in relation to the TATA box might all be plausible explanations for these differences. Transient transfection experiments conducted with a vector carrying mutations in the three TRE sequences indicated that these cis-acting motifs are also important for TCR-CD28-PGE 2 activation is consistent with data from Copeland et al (14). However, our observation that PGE 2 when used alone is a very weak inducer of HTLV-1 transcription in human T cells is in contrast to that of Moriuchi and coworkers (51).…”

Engagement of CD43 Enhances Human Immunodeficiency Virus Type 1 Transcriptional Activity and Virus Production That Is Induced upon TCR/CD3 Stimulation

“…It has been shown that antibody-mediated signaling through the TCR⅐CD3 complex activates HIV-1 transcription and co-engagement of CD28 further augmented virus gene expression (3,4). Interestingly, ligation of CD28 alone is sufficient to induce HIV-1 transcription and replication both in Jurkat cells (5) and in naturally infected leukocytes (6).…”

Engagement of ICAM-3 Provides a Costimulatory Signal for Human Immunodeficiency Virus Type 1 Replication in both Activated and Quiescent CD4+T Lymphocytes: Implications for Virus Pathogenesis

“…Because a number of cis-acting motifs located within the HIV-1 LTR are also found in the regulatory region of genes induced after T-cell activation, extracellular signals that mediate T-cell activation and lymphokine gene expression also regulate HIV-1 gene expression. It has been shown that antibody-mediated signaling through the T-cell receptor (TCR)/CD3 complex activates HIV-1 transcription, and coengagement of the costimulatory molecule CD28 further augments virus gene expression (19,47). An increasing number of accessory cell surface molecules are also involved in upregulation of T-cell activation (reviewed in reference 51).…”