EFFECT OF DIFFERENT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) ISOLATES ON LONG-TERM BONE-MARROW HEMATOPOIESIS

Haemopoietic cytopenias are a frequent occurrence in human immunodefic iency virus type-1 (HIV-1) induced disease. In order to examine the po ssible direct inhibition of marrow haemopoiesis by HIV-1, we have inve stigated the effect of HIV-1 infection on myelopoiesis in long-term bo ne marrow cultures. In vitro exposure of normal marrow cultures to thr ee different lymphocytotropic HIV-1 isolates resulted in productive in fection, as demonstrated by a progressive increase of gag p24 antigen. In these experiments, ICR-3 isolate, but not LAV' or NL4-3 isolates, accelerated the loss of non-adherent cells. A differential ability of these HIV-1 isolates to suppress myelopoiesis was confirmed in long-te rm cultures in which virus was added continuously. In these cultures, ICR-3, and to a lesser extent also NL4-3, but not LAV', induced a prog ressive decrease in the number of total non-adherent cells as well as non-adherent colony forming units-granulocyte/macrophage (CFU-GM). Fur thermore, exposure of normal purified CD34+ cells to ICR-3 induced def ects in their ability to form haemopoietic colonies: this inhibitory e ffect was significantly relieved by pretreatment of ICR-3 with an anti -gp120 antibody. Similar exposure of CD34+ cells to LAV' and NL4-3 ind uced no such defects. These data indicate that some HIV-1 isolates can impair bone marrow haemopoiesis in a dose-dependent fashion, acting, at least in part, at the level of haemopoietic stem/progenitor cells.