HIV-1-related mechanisms of suppression of CD34+ hematopoietic progenitors

Giorgio Zauli, Silvano Capitani

Research output: Contribution to journalArticlepeer-review

Abstract

Peripheral blood cytopenias and bone marrow abnormalities are frequently observed in HIV-l-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 α; (ii) a subset of CD34+ hematopoietic progenitor cells co-expresses the CD4 antigen and maybe infected in vivo with HIV-I; (iii) HIV-I virions or immune complexes containing env gp120 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 β1, 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.

Original languageEnglish
Pages (from-to)53-58
Number of pages6
JournalPathobiology
Volume64
Issue number1
Publication statusPublished - Jan 1996

Keywords

  • Apoptosis
  • CD34+ cells
  • Glycoprotein gp120
  • Human immunodeficiency virus type 1
  • Transforming growth factor β

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Biochemistry
  • Immunology and Allergy
  • Cell Biology

Fingerprint Dive into the research topics of 'HIV-1-related mechanisms of suppression of CD34+ hematopoietic progenitors'. Together they form a unique fingerprint.

Cite this