title: 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.
authors.affiliation: Laboratory of Viral Pathogenesis, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: K F
authors.initials: KF
authors.lastname: Copeland
authors.forename: P J
authors.initials: PJ
authors.lastname: Hendrikx
authors.forename: A G
authors.initials: AG
authors.lastname: Haaksma
authors.forename: S
authors.initials: S
authors.lastname: Fiering
authors.forename: R
authors.initials: R
authors.lastname: Van Lier
authors.forename: J
authors.initials: J
authors.lastname: Goudsmit
authors.forename: J L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D002460:Cell Line; D005822:Genetic Vectors; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D011994:Recombinant Proteins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D016662:Virus Integration; D001616:beta-Galactosidase / Q000096:biosynthesis
chemical_list: D011994:Recombinant Proteins; D001616:beta-Galactosidase