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Journal of Virology, December 2001, p. 11594-11602, Vol. 75, No. 23
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

Hugues Thiebot,1 Fawzia Louache,2 Bruno Vaslin,1 Thierry de Revel,1,3 Olivier Neildez,1 Jérome Larghero,1 William Vainchenker,2 Dominique Dormont,1 and Roger Le Grand1,*

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.


* 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.


Journal of Virology, December 2001, p. 11594-11602, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11594-11602.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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