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Role of human immunodeficiency virus replication in defective in vitro
growth of hematopoietic progenitors
F Louache, A Henri, A Bettaieb, E Oksenhendler, G Raguin, M Tulliez and W Vainchenker
INSERM U. 91, CNRS UA 607, Hopital Henri Mondor, Creteil, France.
A number of hematologic abnormalities, including cytopenias, have been
observed in patients with human immunodeficiency virus (HIV) infection. To
elucidate their mechanisms, a group of 27 patients with HIV-1 infection was
studied. In all patients, a marked reduction of in vitro colony formation
by erythroid, granulomacrophagic, and megakaryocytic bone marrow
progenitors was observed in comparison to normal donors. HIV-1 infection of
marrow progenitors was investigated in studying individual colonies with
the polymerase chain reaction (PCR) technique. No HIV-1 DNA could be
detected in these colonies, suggesting either that marrow progenitors were
not infected or that infected progenitors were not able to generate
colonies in vitro. The addition of antisense oligonucleotides directed
against HIV tat or nef sequences in the culture medium led to a significant
increase in colony formation, suggesting that HIV replication in
hematopoietic progenitors could be responsible for their defective growth.
However, no HIV-1-infected colonies could be detected by PCR after the
antisense treatment, indicating that the increase in colony number was not
due to the proliferation and differentiation of infected progenitors but to
an inhibition of HIV replication in an accessory cell. This last hypothesis
was further confirmed by the absence of effects of antisense oligomers on
the plating efficiency of hematopoietic progenitors grown from CD34+ cells.
These data indicate that hematologic abnormalities of HIV-infected patients
cannot be explained by a direct infection of hematopoietic progenitor cells
and suggest that a defective modulation of progenitor cell growth by HIV
replication outside these cells might play a role in these abnormalities.
Volume 80,
Issue 12,
pp. 2991-2999,
12/15/1992
Copyright © 1992 by The American Society of Hematology
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