Modeling Bone Marrow Progenitor Cell Differentiation and Susceptibility to HIV-1 Infection.

Human immunodeficiency virus type 1 (HIV-1) infection of the monocytic lineage is involved in the pathologic events associated with AIDS and HIV-1-associated dementia (HAD). Hematopoietic progenitor cells (HPCs) within the bone marrow are refractile to HIV-1 infection, while their progeny of the monocyte-macrophage lineage are susceptible. Previous studies, using phorbol-myristate-acetate (PMA) as a differentiating agent, have suggested that the CD34/CD38 TF-1 cell line may be used as one model to study the differentiation processes of HPCs.

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.

Structural and functional evolution of human immunodeficiency virus type 1 long terminal repeat CCAAT/enhancer binding protein sites and their use as molecular markers for central nervous system disease progression.

The appearance and progression of human immunodeficiency virus type 1 (HIV-1)-associated pathogenesis in the immune and central nervous systems is dependent on the ability of the virus to replicate in these compartments, which is, in turn, controlled by numerous factors, including viral binding and entry, receptor and coreceptor usage, and regulation of viral expression by the long terminal repeat (LTR). The LTR promotes viral expression in conjunction with viral and cellular regulatory proteins, including members of the CCAAT/enhancer binding protein (C/EBP) family, which modulate LTR activity through at least two cis-acting binding sites. Previous studies have shown that these sites are necessary for HIV-1 replication in cells of the monocyte/macrophage lineage, but dispensable in T lymphocytes.