NEITHER HUMAN IMMUNODEFICIENCY VIRUS-1 (HIV-1) NOR HIV-2 INFECTS MOST-PRIMITIVE HUMAN HEMATOPOIETIC STEM-CELLS AS ASSESSED IN LONG-TERM BONE-MARROW CULTURES

Attempts to clarify the pathophysiology of human immunodeficiency viru s (HIV)-mediated bone marrow (BM) dysfunction have yielded inconsisten t results regarding the susceptibility of BM progenitors to the viral infection. To specifically address this question, we exposed highly pu rified subpopulations of human BM progenitor cells to various HIV-1 an d HIV-2 strains and assessed (pro)viral gene presence and expression i n more-committed (CD34(+)CD38(+)) as well as most-primitive (CD34(+)CD 38(-)) cells in long-term BM cultures. Quantitative analysis of long-t erm culture-initiating cells (LTCIC) failed to demonstrate adverse eff ects of exposing hematopoietic stem cells to HIV. Our results show tha t HIV-2, similar to HIV-1, does not infect hematopoietic stem cells in vitro with any significant frequency and infected cells are not prese nt within LTCICs. Cytofluorometric analysis of CD34(+) cells for surfa ce molecules that facilitate HIV entry was consistent with the functio nal assay in that expression of virus receptors was predominantly on t he more-committed subsets of BM progenitors. The failure to detect pro ductive or latent HIV in the most-primitive human BM progenitor and st em cells has important implications for future therapeutic strategies, including those dealing with transduction of these cells with protect ive genes as a treatment modality for AIDS. (C) 1998 by The American S ociety of Hematology.