title: HIV-1-related mechanisms of suppression of CD34+ hematopoietic progenitors.
abstract: Peripheral blood cytopenias and bone marrow abnormalities are frequently observed in HIV-1-seropositive subjects. Two major mechanisms have been proposed to explain the hematopoietic failure often observed in patients with advanced HIV-1 disease: (i) infection of cells composing the bone marrow microenvironment with a deranged production of hematopoietic growth factors; (ii) direct suppression of hematopoietic progenitor cells mediated by HIV-1 virions and/or viral proteins. In vivo and in vitro experimental evidence supports a combination of both mechanisms. In fact, it has been shown that: (i) infection with HIV-1 and/or exposure of bone marrow accessory cells to envelope glycoprotein 120 (env gp 120) increases the production of inhibitory cytokines such as tumor necrosis factor alpha; (ii) a subset of CD34+ hematopoietic progenitor cells co-expresses the CD4 antigen and may be infected in vivo with HIV-1; (iii) HIV-1 virions or immune complexes containing env gp 120 are able to induce apoptosis of uninfected CD34+ hematopoietic progenitors. This last inhibitory effect appears to be mediated by the upregulation of transforming growth factor beta 1, which is endogenously produced by hematopoietic progenitors. Both the load and the biological characteristics of the virus play an important role in causing these suppressive effects, since different HIV-1 isolates display varying abilities to suppress hematopoiesis, and some isolates are not cytopathic at all.
authors.affiliation: Institute of Human Anatomy, University of Ferrara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Zauli
authors.forename: S
authors.initials: S
authors.lastname: Capitani
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000472:pathogenicity*; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016867:Immunocompromised Host / Q000276:immunology*
chemical_list: D018952:Antigens, CD34