Transient stimulation of granulopoiesis and drastic inhibition of erythropoiesis in HIV-2-infected long-term liquid bone marrow cultures.
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.
Calenda
V
V
Unite de Recherches INSERM U 322 Sur les Retrovirus et Maladies Associees, Campus Universitaire de Luminy, Marseille, France.
Tamalet
C
C
Chermann
J C
JC
D001853:Bone Marrow / Q000382:microbiology; D001854:Bone Marrow Cells; D002452:Cell Count; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D002999:Clone Cells; D003470:Culture Media; D004920:Erythropoiesis; D006098:Granulocytes / Q000166:cytology*; D015498:HIV-2 / Q000502:physiology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000382:microbiology*; D006801:Humans; D008264:Macrophages / Q000166:cytology; D012194:RNA-Directed DNA Polymerase / Q000032:analysis
D003470:Culture Media; D012194:RNA-Directed DNA Polymerase