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Human Immunodeficiency Virus-1 Infection Interrupts Thymopoiesis
and Multilineage Hematopoiesis In Vivo
Morgan Jenkins,
Mary Beth Hanley,
Mary Beth Moreno,
Eric Wieder, and
Joseph M. McCune
From the Gladstone Institute of Virology and Immunology, San
Francisco, CA; and the Departments of Microbiology and Immunology and
Medicine, University of California, San Francisco, San Francisco,
CA.
It is still uncertain whether multilineage hematopoietic progenitor
cells are affected by human immunodeficiency virus-1 (HIV-1) infection
in vivo. The SCID-hu Thy/Liv model is permissive of long-term
multilineage human hematopoiesis, including T lymphopoiesis. This model
was used to investigate the effects of HIV-1 infection on early
hematopoietic progenitor function. We found that both lineage-restricted and multilineage hematopoietic progenitors were
depleted from grafts infected with either a molecular clone or a
primary isolate of HIV-1. Depletion of hematopoietic progenitors (including CD34+ cells, colony-forming units in
methylcellulose, and long-term culture-initiating cells) occurred
several days before the onset of thymocyte depletion, indicating that
the subsequent rapid decline in thymocyte numbers was due at least in
part to loss of thymocyte progenitors. HIV-1 proviral genomes were not
detected at high frequency in hematopoietic cells earlier than the
intrathymic T-progenitor cell stage, despite the depletion of
such cells in infected grafts. Proviral genomes were also not detected
in colonies derived from progenitor cells from infected grafts. These
data demonstrate that HIV-1 infection interrupts both
lineage-restricted and multilineage hematopoiesis in vivo and suggest
that depletion of early hematopoietic progenitor cells occurs in the
absence of direct viral infection.
Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 2672-2678
© 1998 by The American Society of Hematology.
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