Table 2.
Regulation of HIV-1 gene transcription in primary immune cells and transformed cell lines.
| Transcription Factor | Cell Type | Primary Cells | Transformed Cell Line |
|---|---|---|---|
| NF-κB | T cells | • activates transcription in dopamine-stimulated PBMCs [11] • activates transcription in CD4+ T cells by direct occupancy of enhancer by NF-κB p50/p65 [12] • activates transactivation in TNF-, IL-1-, and IL-7-stimulated TEC co-cultured with thymocytes [13] |
• activates transcription in dopamine-stimulated lymphoid Jurkat T cell line [11] • activates transcription in Jurkat T cell line that stably expresses the Tat [14] • activates transcription in latently HIV-1-infected established T lymphoid cell line J1.1 promoted by MRPs [15] |
| monocytes/macrophages | • activates transcription in macrophages by direct occupancy of enhancer by NF-κB p50/p65 [16] • involved in efficient activation of viral transcription in monocytes isolated from PBMC [17] |
• activates HIV gene transcription in monocytic cell line U937 and promonocytic cell U1 by direct occupancy of enhancer by NF-κB p50/p65 [18,19] | |
| microglial cells | nd | • activates transcription in human microglial MC-3 cell line and embryonic microglial cell line upon stimulation with IFNγ, IL1β, and TNFα [20,21,22] | |
| NF-AT | T cells | • enhances activation of transcription in CD4+ T cells [12] • NF-AT1,2 enhances activation of transcription in PMA/ionomycin stimulated CD4+ T cells [23] • NFAT1, 2 positive effect on transcription in PMA-, PHA-, bpV-stimulated PBMC [24] |
• efficient binding to the HIV-1 LTR enhancer in Jurkat-derived CD4+ T cells isoform CD45(−), stimulated with PMA/PHA/α-CD3 [25] • represses Tat-mediated transactivation in PMA/ionomycin-stimulated Jurkat T-cells [26] • NFAT1, 2 enhances transcription in Jurkat T cells stimulated with PMA, PHA and bpV [24] |
| Sp1, 3 | microglial cells | nd | • Sp1 interaction with COUP-TF leads to activation of HIV gene transcription in microglial cell line [18] • binding CTIP-2 to Sp1 represses Tat-mediated transcriptional activation HIV promoter [27] • Sp3 represses Sp1 and COUP-TF-induced activation in human microglial cell line [18] |
| T cells | • Sp1 associated with Tat activates transcription in CD4+ T cells and PBMCs [12,28] | • Tat-induced Sp1 activates promoter in MT-2 cell line and Jurkat T cells [28] • Sp1 assembly pre-initiation complex at the LTR TATA box and cooperatively interacts with NF-κB to activate transcription in Jurkat T cells stimulated with PMA [29] |
|
| monocytes/macrophages | • Sp1-to-Sp3 ratio increases during monocyte lineage differentiation, resulting in increased HIV-1 transcription [30] | • Sp1 activates LTR-driven transcription in U1 monocytic cells [31] • Sp1 has moderate impact on transcription activation in human monocytic line U-937 [32] |
|
| iDC | • Sp1 activates HIV gene transcription in DC differentiated from monocytes derived from PBMCs [30,33] | nd | |
| AP-1 | microglial cells | nd | • c-jun and c-fos interact with TRE sequence and enhance HIV-1 gene transcription in glial cells [34] |
| monocytes/macrophages | • Vpr-activated AP-1 enhances viral transcription in macrophages differentiated from PBMCs [35] |
• Vpr-activated AP-1 enhances viral transcription in U937 cells [35] • Nuclear complex of c-fos and c-jun binds directly to the HIV LTR and enhances NF-κB activity in human monocytic cell lines U1 and U937 [36] • AP-1 activated by Nef stimulates HIV transcription in U1 and U937 cells [37] |
|
| T cells | • enhances HIV-1 gene expression in CBMCs more than in PBMCs [38] | • c-jun and c-fos do not interact with TRE sequence and do not enhance HIV-1 transcription in Jurkat T cells [34,39] | |
| COUP-TF | microglial cells | • cooperates with Tat to promote NF-κB- and Sp1-independent transactivation HIV-1 transcription in human fetal microglial cells [40] | • cooperates with Tat and promotes NF-κB and Sp1-independent activation HIV-1 transcription in microglial cell line [40] • COUP-TF Sp1 interaction stimulates HIV transcription in microglial cell line [18] • COUP-TF, Sp1, and CTIP2 cooperation suppresses HIV transcription initiation in microglial cells [41] |
| T cells | nd | • COUP-TF interaction with Sp1 synergistically stimulates viral transcription in Jurkat T cells in response to cAMP and dopamine [42] | |
| Ets | T cells | • Ets in cooperation with NF-kB/NFAT activates HIV-1 enhancer in human peripheral blood T cells [43] |
• Ets in cooperation with USF-1 enhances transcriptional activity of HIV-1 LTR in Jurkat T cells [44] |
| C/EBP (NF-IL-6) | monocytes/macrophages | • regulates HIV transcription by recruiting HATs to the LTR in primary macrophages [45] |
• recruits HATs to LTR and mediates initiation of transcription in promonocytic U937 cells [46] |
| T cells | nd | • is not required in HIV transcription in Jurkat CD4+ T cell line [45] • cooperates with CREB and mediates prostaglandin E2-induced stimulation of LTR-driven transcription Jurkat E6.1 [47] |
|
| microglial cells | nd | • in presence of IL-1, IL-6, and TNF- α, activates LTR-driven transcription versus C/EBPγ that acts as inhibitor [48] | |
| CREB | T cells | • phospho-CREB recruits CBP and basal transcription factors, which increases promoter activation in primary lymphocytes [49] | • phospho-CREB recruits CBP and basal transcription factors, which increases promoter activation in MT-4 human T cell line [50] • mediates cAMP and dopamine-induced transcriptional stimulation through indirect interactions with LTR in Jurkat T cells [42] • cooperates with COUP-TF in the presence of forskolin, cAMP, and dopamine to activate HIV-1 gene transcription in Jurkat T cells [42] |
| monocytes/macrophages | nd | • CREB homodimers bind to their DNA site, interact with C/EBPs, and lead to increase HIV promoter activation in U-937 and THP-1 human monocytic cell lines; sequence variations at the CREB site affect LTR activity [51] |
nd, not determined; TEC, human thymic epithelial cell; MRPs, proinflammatory myeloid-related proteins; PBMC, peripheral blood mononuclear cell; NF-AT, nuclear factor of activated T cells; PMA, Phorbol 12-myristate 13-acetate; NF-κB, nuclear factor-kappa B; PHA, phytohemagglutinin; bpV, bis-peroxovana-dium a protein tyrosine phosphatases (PTP) inhibitor; COUP-TF, chicken ovalbumin upstream promoter transcription factor; MT-2, cell line derived from normal human cord leukocytes cocultivated with leukemic cells from an adult T cell leukemia (ATL) patient; CBMCs, umbilical cord blood mononuclear cells; CTIP2, Chicken ovalbumin upstream promoter transcription factor interacting protein 2; cAMP, cyclic AMP, adenosine 3’,5’-cyclic monophosphate; HATs, histone acetylotransferase; Ets, erythroblast transformation specific transcription factor; Sp1, transcription factor specificity protein 1; AP-1, activator protein; C/EBP, CCAAT/enhancer-binding protein; NF-IL-6, transcription factor nuclear factor interleukin 6; CREB, cAMP response element-binding protein; CBP, CREB binding protein.