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Neither Human Immunodeficiency Virus-1 (HIV-1) nor HIV-2 Infects
Most-Primitive Human Hematopoietic Stem Cells as Assessed in
Long-Term Bone Marrow Cultures
Frank F. Weichold,
Davide Zella,
Oxana Barabitskaja,
Jaroslaw P. Maciejewski,
Daniel E. Dunn,
Elaine M. Sloand, and
Neal S. Young
From the Institute of Human Virology, University of Maryland,
Baltimore; the Department of Internal Medicine, University of Nevada,
School of Medicine, Reno; and the Hematology Branch, National Heart,
Lung and Blood Institute, Bethesda, MD.
Attempts to clarify the pathophysiology of human immunodeficiency
virus (HIV)-mediated bone marrow (BM) dysfunction have yielded inconsistent results regarding the susceptibility of BM progenitors to
the viral infection. To specifically address this question, we exposed
highly purified subpopulations of human BM progenitor cells to various
HIV-1 and HIV-2 strains and assessed (pro)viral gene presence and
expression in more-committed (CD34+CD38+)
as well as most-primitive (CD34+CD38 )
cells in long-term BM cultures. Quantitative analysis of long-term culture-initiating cells (LTCIC) failed to demonstrate adverse effects
of exposing hematopoietic stem cells to HIV. Our results show that
HIV-2, similar to HIV-1, does not infect hematopoietic stem cells in
vitro with any significant frequency and infected cells are not present
within LTCICs. Cytofluorometric analysis of CD34+ cells
for surface molecules that facilitate HIV entry was consistent with the
functional assay in that expression of virus receptors was
predominantly on the more-committed subsets of BM progenitors. The
failure to detect productive or latent HIV in the most-primitive human
BM progenitor and stem cells has important implications for future
therapeutic strategies, including those dealing with transduction of
these cells with protective genes as a treatment modality for AIDS.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 907-915
© 1998 by The American Society of Hematology.
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