C/EBP- and Tat-mediated activation of the HIV-1 LTR in CD34+ hematopoietic progenitor cells

Human immunodeficiency virus type 1 (HIV-1) infection of cells of the monocyte/macrophage lineage within the bone marrow and peripheral blood plays an important role in the pathologic events leading to the development of the acquired immune deficiency syndrome (AIDS) as well as HIV-1 dementia (HIVD). The TF-1 erythro-myeloid cell line is being utilized as a model cellular phenotype to examine HIV-1 infection of a hematopoietic progenitor cell population. Expression of TF- 1 cell surface marker RNAs and proteins was characterized by RT-PCR and FACS, respectively, and compared to those of the well characterized U-937 monocytic cell line. Transcription factors in TF-1 and U-937 cells that have been shown to be important for sustaining the expression of HIV-1 LTR activity were also examined. TF- 1 cells were shown to contain the transcription factors C/EBP, Spl, and NF-KB. C/EBP- and Tat-mediated induction of the YU-2 LTR was examined. Relative C/EBP induction of the HIV-1 strain YU-2 LTR was greater in TF- 1 cells than in U-937 cells. When the C/EBP sites I and II were mutated to sequences with a low relative affinity for C/EBP factors, there was a reduction of Tat-mediated trans-activation in TF-1 cells, but not in U-937 cells. These studies form the foundation for investigations into the relationship between HIV-1 infection of bone marrow and peripheral blood precursor cells of the monocyte/macrophage lineage and pathogenesis associated with HIV-1 infection of the immune and central nervous system (CNS).