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Updated: Jul 14, 2026
Retroviral Transduction of Bone Marrow Progenitor Cells to Generate T-cell Receptor Retrogenic Mice
Published on: July 11, 2016
PMA-induced differentiation of a bone marrow progenitor cell line activates HIV-1 LTR-driven transcription
Aikaterini Alexaki1, Shane J Quiterio, Yujie Liu
1Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
Abstract:
Cells of the monocyte-macrophage lineage play an important role in human immunodeficiency virus type 1 (HIV-1)-associated disease. Infected myeloid precursor cells of the bone marrow are thought to be a viral reservoir that may repopulate the peripheral blood, central nervous system (CNS), and other organ systems throughout the course of disease. To model select aspects of HIV-1 infection of the bone marrow compartment in vitro, the erythro-myeloid precursor cell line, TF-1, was used. Phorbol 12-myristate 13-acetate (PMA) was found to induce the TF-1 cell line to differentiate through the myeloid lineage and become activated, as demonstrated by cellular morphologic changes and surface expression of differentiation and activation markers. Herein we demonstrate that HIV-1 long terminal repeats (LTRs) from T-, M-, and dual-tropic molecular clones have similar basal LTR activity in TF-1 cells and that differentiation of these cells by PMA resulted in increased LTR activity. Examination of specific cis-acting elements involved in basal and PMA-induced LTR activity demonstrated that the transcription factor families nuclear factor-kappa B (NF-kappaB) and specificity protein (Sp) contributed to the LTR activity of TF-1 cells, the Sp family being the most critical. These studies elucidate the impact of infected bone marrow monocytic cell differentiation on LTR activity and its potential impact on HIV-1-associated disease.
Insights
Human immunodeficiency virus type 1 (HIV-1) bone marrow infection involves myeloid precursor cells. Cell differentiation increases viral long terminal repeat (LTR) activity, influenced by transcription factors.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Monocyte-macrophage lineage cells are crucial in human immunodeficiency virus type 1 (HIV-1) pathogenesis.
- Bone marrow myeloid precursor cells are a potential viral reservoir, contributing to systemic infection.
- In vitro models are needed to study HIV-1 infection in the bone marrow microenvironment.
Purpose of the Study:
- To model HIV-1 infection of bone marrow myeloid precursor cells in vitro using the TF-1 cell line.
- To investigate the effect of myeloid differentiation on HIV-1 long terminal repeat (LTR) activity.
- To identify cis-acting elements regulating LTR activity in differentiating myeloid cells.
Main Methods:
- Utilized the TF-1 erythro-myeloid precursor cell line.
- Induced myeloid differentiation and activation using Phorbol 12-myristate 13-acetate (PMA).
- Assessed HIV-1 LTR activity and analyzed the role of transcription factors NF-kappaB and Sp.
Main Results:
- PMA induced TF-1 cell differentiation and activation, confirmed by morphological changes and marker expression.
- HIV-1 LTRs from various clones showed similar basal activity in TF-1 cells.
- PMA-induced differentiation significantly increased HIV-1 LTR activity, with the Sp family being critical.
Conclusions:
- Myeloid cell differentiation in the bone marrow enhances HIV-1 LTR activity.
- Transcription factors, particularly the Sp family, play a key role in regulating LTR activity during differentiation.
- These findings provide insights into HIV-1 pathogenesis and the role of the bone marrow reservoir.
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