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Journal of Virology, December 2001, p. 11594-11602, Vol. 75, No. 23
CEA, Service de Neurovirologie, CRSSA, Ecole
Pratique des Hautes Etudes, Institut Paris-Sud sur les Cytokines, 92 265 Fontenay aux Roses Cedex,1
Unité de Recherche en Hématologie et Cellules
Souches, INERM 392, Institut Gustave Roussy, 94 805 Villejuif,2 and Hopital d'Instruction
des Armées Percy, 92 141 Clamart Cedex,3
France
Received 30 May 2001/Accepted 30 August 2001
The hematological abnormalities observed in human immunodeficiency
virus (HIV)-infected patients appear to be mainly due to bone marrow
dysfunction. A macaque models of AIDS could greatly facilitate an in
vivo approach to the pathogenesis of such dysfunction. Here, we
evaluated in this model the impact of infection with a pathogenic
simian/human immunodeficiency virus (SHIV) on bone marrow
hematopoiesis. Three groups of macaques were inoculated with 50 50%
median infective doses of pathogenic SHIV 89.P, which expresses
env of dual-tropic HIV type 1 (HIV-1) 89.6 primary
isolate. During the primary phase of infection, animals were treated
with either a placebo or highly active antiretroviral therapy (HAART) combining zidovudine, lamivudine, and indinavir, initiated 4 or 72 h postinfection (p.i.) and administered twice a day until day 28 p.i. In both placebo-treated and HAART-treated animals, bone marrow
colony-forming cells (CFC) progressively decreased quite early, during
the first month p.i. One year p.i., both placebo- and HAART-treated
animals displayed decreases in CFC to about 56% of preinfection
values. At the same time, a dramatic decrease (greater than 77%) of
bone marrow CD34+ long-term culture-initiating cells was
noted in all animals were found. No statistically significant
differences between placebo- and HAART-treated monkeys were found.
These data argue for an early and profound alteration of myelopoiesis
at the level of the most primitive CD34+ progenitor cells
during SHIV infection, independently of the level of viremia,
circulating CD4+ cell counts, or antiviral treatment.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.23.11594-11602.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Early and Persistent Bone Marrow Hematopoiesis
Defect in Simian/Human Immunodeficiency Virus-Infected Macaques despite
Efficient Reduction of Viremia by Highly Active Antiretroviral Therapy
during Primary Infection
*
Corresponding author. Mailing address: Service de
Neurovirologie, Commissariat à l'Energie Atomique,
DSV/DRM/CRSSA, 60-68 Ave. de la Division Leclerc, B.P. 6, 92265 Fontenay-aux-Roses Cedex, France. Phone: 33 1 46 54 73 74. Fax: 33 1 46 54 77 26. E-mail: legrand{at}dsvidf.cea.fr.
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