INHIBITORY EFFECTS OF HIV-1-INFECTED STROMAL CELL-LAYERS ON THE PRODUCTION OF MYELOID PROGENITOR CELLS IN HUMAN LONG-TERM BONE-MARROW CULTURES

This report presents the results of studies using long-term bone marro w cultures (LTBMC) of human bone marrow cells to investigate the effec t of HIV-1 on in vitro hematopoiesis. Confluent stromal cell layers es tablished from human bone marrow cells were irradiated to eliminate re sidual hematopoietic progenitor cells and exposed to HIV-1(ADA) or to HIV-1(IIIB), monocytotropic and lymphocytotropic strains of HTV-1, res pectively. A productive infection did not develop in cultures exposed to HIV-1(IIIB) but did for cultures exposed to HIV-1(ADA) as there was a progressive increase in HIV-1 p24 antigen. Stromal cell layers infe cted with HIV-1(ADA) were also cocultured with autologous CD34(+) bone marrow cells. Four days, 1, 2, and 3 weeks later, the number of colon y-forming units granulocyte/macrophage (CFU-GM) in non- and HIV-infect ed LTBMC was determined. The number of CFU-GM increased during the fir st week in both non- and HN-infected LTBMC. One week after the cocultu re of CD34(+) cells with stromal cell layers infected with HIV-1(ADA), the number of CFU-GM in six out of eight experiments was reduced comp ared to noninfected control LTBMC. In those six experiments, the numbe r of CFU-GM was 53 +/- 6% standard error of the mean (SEM) of the numb er in noninfected LTBMC. A reduced number of CFU-GM was observed in th e nonadherent fraction of HIV-infected LTBMC for at least 2 weeks. The se results demonstrate that some cells in the stromal cell layers of L TBMC were targets for HIV-1 and that HIV-infected stromal cell layers suppressed or delayed the production of CFU-GM.