Infection and replication of HIV-1 in purified progenitor cells of normal human bone marrow.
Myeloid progenitor cells were highly purified from normal human bone marrow by positive immunoselection with high-affinity monoclonal antibodies linked to magnetic beads and were successfully infected in vitro with the human immunodeficiency virus type 1 (HIV-1). From 99 to 100 percent pure bone marrow cells expressing the CD34 phenotypic marker were obtained. These cells were devoid of mature myeloid or T cell surface and intracellular markers as analyzed by immunohistochemical staining and flow cytometry. HIV-1 particles were detected by supernatant reverse transcriptase activity and transmission electron microscopy 40 to 60 days after infection. Viral particles were predominantly observed assembling and accumulating from within intracellular membranes, while phenotypically the cells were observed to have differentiated into CD4+ monocytes. These studies have important implications in understanding the pathogenesis of HIV-1 as well as the possible cause of certain of the observed hematologic abnormalities in HIV-1 infection. They also indicate that the bone marrow may serve as a potentially important reservoir of HIV-1 in the body.
Folks
T M
TM
Laboratory of Immunoregulation, National Institutes of Health, Bethesda, MD 20892.
Kessler
S W
SW
Orenstein
J M
JM
Justement
J S
JS
Jaffe
E S
ES
Fauci
A S
AS
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D001854:Bone Marrow Cells; D002462:Cell Membrane / Q000382:microbiology; D002469:Cell Separation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006678:HIV / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000382:microbiology* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D010641:Phenotype; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D014779:Virus Replication
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D012194:RNA-Directed DNA Polymerase