title: CD34+ and CFU-GM progenitors are significantly decreased in SIVsmm9 infected rhesus macaques with minimal evidence of direct viral infection by polymerase chain reaction.
abstract: Hematologic abnormalities in the peripheral blood and bone marrow are associated with human immunodeficiency and simian immunodeficiency virus (HIV, SIV) infection. The reasons for these abnormalities remain unclear. Bone marrow specimens collected from uninfected animals (Group A, Controls) and from rhesus macaques experimentally infected with SIVsmm9 during the asymptomatic stage (Group B, SIV+ "well") and during the clinically ill stage (Group C, SIV+ "sick"), underwent a variety of in vitro assays of hematopoiesis. Colony forming unit-granulocyte/macrophage (CFU-GM) per plate growth was 46.7 +/- 7.7, 31.9 +/- 8.4 and 6.5 +/- 5.0 (mean +/- sd, P < .02 each mean compared to the others) in the 3 groups respectively. Burst forming unit-erythroid (BFU-E) growth was similarly decreased in bone marrow samples from the SIV+ animals. There was no change in the number of CFU-GM per plate with the removal of plastic adherent or T-cell mononuclear cell fractions. There was no increase in CFU-GM per plate growth with the addition of low dose GM-CSF (1 or 5 ng/mL) though there was a near 67% increase (48 to 80 CFU-GM per plate) with the addition of 100 ng/mL recombinant rhesus IL-3 and 100 ng/mL GM-CSF in SIV+ "sick" animals. Variation in frequency of CD34+ progenitor cells in SIV+ animals was seen, with 3.0% CD34+ cells in SIV- controls, 4.9% CD34+ cells in SIV+ "well" animals and 0.5% CD34+ progenitor cells in SIV+ "sick" monkeys (P < .01, each mean compared to the others). Finally, there was minimal evidence of SIV sequences by polymerase chain reaction in pooled cultured CFU-GM, and no evidence in flowcytometrically sorted CD34+ progenitor cells from selected animals. Thus, the SIV seropositive rhesus monkey appears to have similar hematopoietic aberrations as are found in HIV infected human subjects and may be an excellent model for studying the interaction of lentiviruses on the kinetics of blood formation.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: C D
authors.initials: CD
authors.lastname: Hillyer
authors.forename: D A
authors.initials: DA
authors.lastname: Lackey
authors.forename: F
authors.initials: F
authors.lastname: Villinger
authors.forename: E F
authors.initials: EF
authors.lastname: Winton
authors.forename: H M
authors.initials: HM
authors.lastname: McClure
authors.forename: A A
authors.initials: AA
authors.lastname: Ansari
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000276:immunology / Q000473:pathology; D006400:Hematocrit; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000175:diagnosis / Q000276:immunology / Q000473:pathology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000502:physiology
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D004279:DNA, Viral; D016178:Granulocyte-Macrophage Colony-Stimulating Factor