Transient stimulation of granulopoiesis and drastic inhibition of erythropoiesis in HIV-2-infected long-term liquid bone marrow cultures
Calenda, V.; Tamalet, C.; Chermann, J.C.
Journal of Acquired Immune Deficiency Syndromes 5(11): 1148-1157
1992
ISSN/ISBN: 0894-9255 PMID: 1383491 Document Number: 389630
Impaired hematopoiesis is commonly associated with human immunodeficiency virus HIV-1 and HIV-2-related AIDS. HIV-1 infection of hematopoietic progenitors has been studied, whereas HIV-2 infection of these cells is less well documented. In this work, we studied myeloid and erythroid progenitor production and differentiation in long-term bone marrow (LTBM) cultures after HIV-2 infection. A nonadherent fraction from these cultures containing the hematopoietic progenitors is nonproductively infected with HIV-2, whereas stroma cells replicate the virus only weakly. HIV-2 can be rescued from nonadherent T-depleted bone marrow cells, and its replication in stroma cells is amplified by cocultivation with HIV permissive cells. Colony assays performed weekly during the 6 weeks of LTBM cultures revealed a 100% inhibition of erythroid colony-forming unit (CFU)-E and erythroid burst-forming unit (BFU)-E production after 12 days of culture, whereas granulomonocytic colony forming units (CFU-GM) production was stimulated until day 20 and then disappeared on day 30. Stimulatory and inhibitory activities were recovered from supernatants of infected LTBM cultures and an infected lymphoid CEM cell line, suggesting that release of viral factor(s) may be responsible for HIV-2-induced impairment of hematopoietic progenitor production in vitro. Based on these results, an indirect effect of HIV-2 infection on the commitment of myeloid and erythroid progenitors, resulting in a dysregulated hematopoiesis, is postulated.