scholarly journals T Cell Activation and Regulation of HIV-1: Same Effectors with Distinct Outcomes

1999 ◽  
Vol 10 (suppl c) ◽  
pp. 25C-32C ◽  
Author(s):  
Jean-François Fortin ◽  
Benoit Barbeau ◽  
Gilles A Robichaud ◽  
Michel J Tremblay
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Immune System ◽  
Virus Replication ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Nuclear Factor ◽  
Cellular Transcription ◽  
Hiv 1

The molecular mechanisms that regulate the function of the immune system and human immunodeficiency virus type-1 (HIV-1) gene expression are diverse and complicated. However, replication of HIV-1 is controlled by many of the same regulatory signals that play a crucial role in the transcriptional regulation of the immune system. For example, the viral promoter, as is the case for the immune system, is subject to complex regulation by combinations of cellular transcription factors that may quantitatively and/or qualitatively differ depending on cell types (eg, macrophages versus T lymphocytes) and cell states (eg, undifferentiated versus differentiated or quiescent versus activated). The present review discusses the regulation of HIV-1 gene expression by nuclear factor-kappa Band nuclear factor of activated T cells, and proposes that selective interference of these two cellular transcription factors may be a route to abrogate virus replication without disrupting normal cellular functions. A better understanding of the regulation of HIV-1 gene expression is of utmost importance for the design of molecular approaches that will effectively abrogate virus replication and, ultimately, disease progression.

Regulation of HIV-1 Gene Expression by Cellular Transcription Factors

Pathobiology ◽  
1992 ◽  
Vol 60 (4) ◽  
pp. 219-224 ◽  
Author(s):  
Premkumar Ready ◽  
Purandar Dasgupta
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Cellular Transcription ◽  
Hiv 1

scholarly journals Early Pro-Inflammatory Signal and T-Cell Activation Associate With Vaccine-Induced Anti-Vaccinia Protective Neutralizing Antibodies

2021 ◽  
Vol 12 ◽  
Author(s):  
Jue Hou ◽  
Shuhui Wang ◽  
Dan Li ◽  
Lindsay N. Carpp ◽  
Tong Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Neutralizing Antibodies ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Neutralizing Antibody ◽  
Activator Protein 1 ◽  
Successful Vaccine ◽  
Hiv 1 ◽  
Core Genes

Both vaccine “take” and neutralizing antibody (nAb) titer are historical correlates for vaccine-induced protection from smallpox. We analyzed a subset of samples from a phase 2a trial of three DNA/HIV-1 primes and a recombinant Tiantan vaccinia virus-vectored (rTV)/HIV-1 booster and found that a proportion of participants showed no anti-vaccinia nAb response to the rTV/HIV-1 booster, despite successful vaccine “take.” Using a rich transcriptomic and vaccinia-specific immunological dataset with fine kinetic sampling, we investigated the molecular mechanisms underlying nAb response. Blood transcription module analysis revealed the downregulation of the activator protein 1 (AP-1) pathway in responders, but not in non-responders, and the upregulation of T-cell activation in responders. Furthermore, transcriptional factor network reconstruction revealed the upregulation of AP-1 core genes at hour 4 and day 1 post-rTV/HIV-1 vaccination, followed by a downregulation from day 3 until day 28 in responders. In contrast, AP-1 core and pro-inflammatory genes were upregulated on day 7 in non-responders. We speculate that persistent pro-inflammatory signaling early post-rTV/HIV-1 vaccination inhibits the nAb response.

Regulation of 4F2 heavy-chain gene expression during normal human T-cell activation can be mediated by multiple distinct molecular mechanisms

1988 ◽  
Vol 8 (9) ◽  
pp. 3820-3826
Author(s):  
T Lindsten ◽  
C H June ◽  
C B Thompson ◽  
J M Leiden
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Steady State ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Transcription Elongation ◽  
Fold Increase ◽  
Mrna Levels ◽  
Myristate Acetate

The 4F2 molecule belongs to the set of cell surface antigens which is induced following lectin- or antigen-mediated T-cell activation. The increase in 4F2 cell surface expression following lectin-mediated stimulation has been shown to be accompanied by a parallel increase in the steady-state levels of 4F2 heavy-chain (4F2HC) mRNA. The studies described in this report were designed to further elucidate the molecular mechanisms responsible for induction of 4F2HC gene expression following activation of normal resting human peripheral blood T cells. The low levels of mature 4F2HC mRNA in resting T cells were shown to be the result of a block to transcription elongation within the exon 1-intron 1 region of the 4F2HC gene rather than promoter inactivity. Phorbol myristate acetate stimulation of resting T cells resulted in a 20-fold increase in steady-state 4F2HC mRNA levels which was mediated by removal of this block to transcription elongation. The phorbol myristate acetate-induced increase in 4F2HC gene expression is distinct from previously described AP-1-mediated, phorbol ester-induced gene expression in that it requires new protein synthesis. Treatment of resting T cells with ionomycin plus PMA resulted in a 60-fold increase in 4F2HC mRNA levels. This induction was mediated by both an increase in promoter utilization and removal of the block to transcription elongation. Finally, by increasing the half-life of 4F2HC mRNA, cycloheximide treatment of resting T cells induced an approximately five fold increase in the levels of 4F2HC gene expression, although the physiologic significance of this mechanism remains unclear. These results demonstrate that the level of 4F2HC gene expression in normal peripheral blood T cells can be regulated by at least three distinct molecular pathways: (i) changes in promoter utilization, (ii) modulation of a block to transcription elongation, and (iii) alteration in mRNA stability.

scholarly journals Regulation of 4F2 heavy-chain gene expression during normal human T-cell activation can be mediated by multiple distinct molecular mechanisms.

1988 ◽  
Vol 8 (9) ◽  
pp. 3820-3826 ◽  
Author(s):  
T Lindsten ◽  
C H June ◽  
C B Thompson ◽  
J M Leiden
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Steady State ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Transcription Elongation ◽  
Fold Increase ◽  
Mrna Levels ◽  
Myristate Acetate

The 4F2 molecule belongs to the set of cell surface antigens which is induced following lectin- or antigen-mediated T-cell activation. The increase in 4F2 cell surface expression following lectin-mediated stimulation has been shown to be accompanied by a parallel increase in the steady-state levels of 4F2 heavy-chain (4F2HC) mRNA. The studies described in this report were designed to further elucidate the molecular mechanisms responsible for induction of 4F2HC gene expression following activation of normal resting human peripheral blood T cells. The low levels of mature 4F2HC mRNA in resting T cells were shown to be the result of a block to transcription elongation within the exon 1-intron 1 region of the 4F2HC gene rather than promoter inactivity. Phorbol myristate acetate stimulation of resting T cells resulted in a 20-fold increase in steady-state 4F2HC mRNA levels which was mediated by removal of this block to transcription elongation. The phorbol myristate acetate-induced increase in 4F2HC gene expression is distinct from previously described AP-1-mediated, phorbol ester-induced gene expression in that it requires new protein synthesis. Treatment of resting T cells with ionomycin plus PMA resulted in a 60-fold increase in 4F2HC mRNA levels. This induction was mediated by both an increase in promoter utilization and removal of the block to transcription elongation. Finally, by increasing the half-life of 4F2HC mRNA, cycloheximide treatment of resting T cells induced an approximately five fold increase in the levels of 4F2HC gene expression, although the physiologic significance of this mechanism remains unclear. These results demonstrate that the level of 4F2HC gene expression in normal peripheral blood T cells can be regulated by at least three distinct molecular pathways: (i) changes in promoter utilization, (ii) modulation of a block to transcription elongation, and (iii) alteration in mRNA stability.

scholarly journals Nfat

2002 ◽  
Vol 156 (5) ◽  
pp. 771-774 ◽  
Author(s):  
Valerie Horsley ◽  
Grace K. Pavlath
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Transcription Factors ◽  
Immune System ◽  
Cell Types ◽  
Cytokine Gene Expression ◽  
Nuclear Factor ◽  
Cytokine Gene ◽  
Activated T Cells ◽  
Control Of Gene Expression

The nuclear factor of activated T cells (NFAT) proteins are a family of transcription factors whose activation is controlled by calcineurin, a Ca2+-dependent phosphatase. Originally identified in T cells as inducers of cytokine gene expression, NFAT proteins play varied roles in cells outside of the immune system. This review addresses the recent data implicating NFAT in the control of gene expression influencing the development and adaptation of numerous mammalian cell types.

scholarly journals A Praziquantel Treatment Study of Immune and Transcriptome Profiles in Schistosoma haematobium-Infected Gabonese Schoolchildren

2019 ◽  
Vol 222 (12) ◽  
pp. 2103-2113
Author(s):  
Lucja A Labuda ◽  
Ayola A Adegnika ◽  
Bruce A Rosa ◽  
John Martin ◽  
Ulysse Ateba-Ngoa ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
T Cell Activation ◽  
Schistosoma Haematobium ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Effector Memory ◽  
Schistosome Infection ◽  
Adaptive Immune ◽  
Praziquantel Treatment

Abstract Background Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms. Methods Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed. Results Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were negatively associated with CD4+CD25+FOXP3+ T-cells and accompanied by increased frequency of effector memory T-cells. Innate responses to Toll like receptor (TLR) ligation decreased with treatment and showed positive association with CD4+CD25+FOXP3+ T-cells. At the transcriptome level, schistosome infection was associated with enrichment in cell adhesion, whereas parasite removal was associated with a more quiescent profile. Further analysis indicated that alteration in cellular energy metabolism was associated with S haematobium infection and that the early growth response genes 2 and 3 (EGR 2 and EGR3), transcription factors that negatively regulate T-cell activation, may play a role in adaptive immune hyporesponsiveness. Conclusions Using a longitudinal study design, we found contrasting effects of schistosome infection on innate and adaptive immune responses. Whereas the innate immune system appears more activated, the adaptive immunity is in a hyporesponsive state reflected in alterations in CD4+CD25+FOXP3+ T-cells, cellular metabolism, and transcription factors involved in anergy.

scholarly journals The T Cell Activation Factor NF-ATc Positively Regulates HIV-1 Replication and Gene Expression in T Cells

Immunity ◽  
1997 ◽  
Vol 6 (3) ◽  
pp. 235-244 ◽  
Author(s):  
Shigemi Kinoshita ◽  
Lishan Su ◽  
Masahiko Amano ◽  
Luika A Timmerman ◽  
Hideto Kaneshima ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Activation Factor ◽  
Hiv 1
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