Experimental infection of macaques with pathogenic strains of simian immunodeficiency virus (SIV) represents one of the most relevant animal models for studying HIV pathogenesis. In this study, we demonstrated a significant decrease in the generation of CD4(+) T cells from bone marrow (BM) CD34(+) progenitors in macaques infected with SIVmac251. This decrease appears to result from changes in the clonogenic potential of BM progenitors of both the myeloid and lymphoid lineages. We also demonstrated a significant decrease in the numbers of the most immature long-term culture-initiating cells (LTC-ICs). Hematopoietic failure occurred as early as primary infection, in the absence of CD34(+) BM cell infection and was not related to plasma viral load. No major change was observed in the phenotype of BM CD34(+) cells from infected macaques, including apoptosis markers such as annexin V staining and BcL-2 expression, buta significantly higher that normal proportion of cells were in the G(0)/G(1) phase. This is the first demonstration that failure of BM hematopoiesis results in impaired T-cell production, which may contribute to the disruption of T-lymphocyte homeostasis characteristic of pathogenic lentiviral infections in primates. (c) 2005 by The American Society of Hematology.
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