PMA-induced differentiation of a bone marrow progenitor cell line activates HIV-1 LTR-driven transcription.
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.
Alexaki
Aikaterini
A
Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
Quiterio
Shane J
SJ
Liu
Yujie
Y
Irish
Bryan
B
Kilareski
Evelyn
E
Nonnemacher
Michael R
MR
Wigdahl
Brian
B
D015703:Antigens, CD / Q000378:metabolism; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D016297:Mutagenesis, Site-Directed; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism; D051703:Sp Transcription Factors / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D015703:Antigens, CD; D022762:CCAAT-Enhancer-Binding Proteins; D004279:DNA, Viral; D016328:NF-kappa B; D051703:Sp Transcription Factors; D013755:Tetradecanoylphorbol Acetate