Role of HIV-1 in the functional impairment of CD34(+) hematopoietic progenitor cells

The role played by HIV-1 infection in the pathogenesis of peripheral blood cytopenias frequently found in HIV-1 seropositive individuals was initially elusive. However, a body of in vivo and in vitro experimental evidence suggests that HIV-I can be directly involved in the suppression of hematopoietic progenitor cells through either direct or indirect mechanisms: (1) infection (productive or non-productive) of a subset of CD34(+) hematopoietic progenitor cells, co-expressing the CD4 antigen with growth defects of infected cells; (2) membrane interactions of CD34(+) hematopoietic progenitor cells with HIV-1 virions or immune complexes containing env gp120, which can directly lead CD34(+) cells to apoptotic cell death. Both the viral load and the biological characteristics of the virus play an important role in causing these suppressive effects, since different isolates displayed a differential ability to suppress hematopoiesis; (3) infection with HIV-1 and/or exposure of bone marrow accessory cells to viral proteins (gp120 and Tat) with increased production of inhibitory factors, such as TNF-alpha or TGF-beta 1.