title: Impact of bone marrow hematopoiesis failure on T-cell generation during pathogenic simian immunodeficiency virus infection in macaques.
abstract: 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, but a significantly higher that normal proportion of cells were in the G0/G1 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.
authors.affiliation: CEA, Laboratoire d'Immuno-Pathologie Expérimentale, Service de Neurovirologie, Centre de Recherches du Service de Santé des Armées, Ecole Pratique des Hautes Etudes, Institut Paris-Sud sur les Cytokines, Université Paris XI, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Thiebot
authors.forename: Bruno
authors.initials: B
authors.lastname: Vaslin
authors.forename: Sonia
authors.initials: S
authors.lastname: Derdouch
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Bertho
authors.forename: Franck
authors.initials: F
authors.lastname: Mouthon
authors.forename: Stéphane
authors.initials: S
authors.lastname: Prost
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gras
authors.forename: Pierre
authors.initials: P
authors.lastname: Ducouret
authors.forename: Dominique
authors.initials: D
authors.lastname: Dormont
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000097:blood; D018952:Antigens, CD34; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000821:virology; D016193:G1 Phase; D005786:Gene Expression Regulation; D019254:Genes, bcl-2; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000821:virology; D006706:Homeostasis; D038041:Lymphopoiesis; D008252:Macaca fascicularis / Q000097:blood* / Q000821:virology; D008297:Male; D008992:Monkey Diseases / Q000097:blood* / Q000473:pathology / Q000821:virology; D038042:Myelopoiesis; D016192:Resting Phase, Cell Cycle; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000473:pathology; D015302:Simian Immunodeficiency Virus; D019562:Viral Load
chemical_list: D017304:Annexin A5; D018952:Antigens, CD34