In vitro suppression of normal human bone marrow progenitor cells by human immunodeficiency virus.
Incubation of normal human nonadherent and T-cell-depleted bone marrow cells with HIVIIIB at multiplicities of infection (MOI) ranging from 0.0001:1 to 1:1 reverse transcriptase (RT) units resulted in the dose-dependent suppression of the in vitro growth of erythroid burst-forming unit (BFU-E), granulocyte-macrophage (CFU-GM), and T-lymphocyte (CFU-TL) colonies of progenitor cells. Maximum inhibition of colony formation was observed at a 1:1 ratio of virus to bone marrow cells. At this MOI, BFU-E and CFU-GM colonies were inhibited by 60 to 80%, while CFU-TL colonies were totally suppressed. Inhibition of colony formation was also observed at an MOI of 0.1:1 but not with further log dilutions of the virus. Incubation of the virus with antibody to gp160 resulted in the complete reversal of stem cell suppression and the normalization of colony growth in vitro. For BFU-E and CFU-GM colonies, this reversal was observed with dilutions of antibody up to 1:100 and was no longer observed at titers greater than 1:500. The CFU-TL colony number normalized at titers between 1:10 and 1:50. Human immunodeficiency virus (HIV) also suppressed by 50% the growth of colonies derived from CD34+ stem cell fractions. Infection of CD34+ cells and T-cell-depleted, nonadherent cell fractions was demonstrated by detection with HIV-specific DNA probe following amplification by polymerase chain reaction. The results suggest that HIV can directly infect human bone marrow progenitor cells and affect their ability to proliferate and give rise to colonies in vitro. The results indicate a direct role for the virus in bone marrow suppression and a possible mechanism for the cytopenias observed in patients with AIDS.
Steinberg
H N
HN
Harvard Thorndike Laboratory, Charles A. Dana Research Institute, Division of Hematology/Oncology, Beth Israel Hospital, Boston, Massachusetts.
Crumpacker
C S
CS
Chatis
P A
PA
D001853:Bone Marrow / Q000382:microbiology; D002455:Cell Division; D003114:Colony-Forming Units Assay; D015342:DNA Probes; D015686:Gene Products, env / Q000276:immunology; D006678:HIV / Q000276:immunology / Q000502:physiology*; D019302:HIV Envelope Protein gp160; D015658:HIV Infections / Q000382:microbiology*; D006412:Hematopoietic Stem Cells / Q000382:microbiology* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007958:Leukocyte Count; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000382:microbiology; D014779:Virus Replication
D015342:DNA Probes; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors