HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION IMPAIRS HEMATOPOIESIS IN LONG-TERM BONE-MARROW CULTURES - NONREVERSAL BY NUCLEOSIDE ANALOGS

Hematologic abnormalities are often seen in patients infected with hum an immunodeficiency virus (HIV). The effect of HIV infection of bone m arrow stroma on support of uninfected CD34 progenitor cells in long-te rm bone marrow culture (LTBMC) was investigated, Results show that HIV -infected bone marrow stroma was unable to adequately support CD34 pro genitor cells in vitro. Zidovudine or didanosine was added to cultures in an attempt to reverse the suppressive effects exerted by HIV and t o determine whether such suppression was mediated by transfer of HIV i nfection to progenitor cells. Didanosine failed to reduce the suppress ive effects of HIV, whereas zidovudine compounded the observed suppres sion. HIV infection of bone marrow stroma, while reducing the producti on of nonadherent cells, did not increase apoptosis and cell death in such cells, In contrast, zidovudine enhanced apoptosis and cell death in nonadherent cells produced by both HIV-infected and control LTBMC.