Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
Numbers of functional bone marrow colony-forming cells decrease late in SIV infection of rhesus monkeys.
Symp Nonhum Primate Models AIDS. 1990 Nov 28-30;8:38 (abstract no. 22). Unique Identifier : AIDSLINE PRIM8/900022 Beltz LA; Narayan O; Adams RJ; Zink MC; Donnenberg AD; The Johns Hopkins University, School of Medicine, Baltimore, MD
Abstract:
We have used a long term bone marrow (BM) culture system to estimate progenitor frequency by limiting dilution analysis (LDA) in 7 Rhesus macaques studied before and after infection with SIV251. BM cells were first separated on a Ficoll/Hypaque gradient, then depleted of T lymphocytes plus early and mature monocyte/macrophages and granulocytes by 2 rounds of antibody-complement mediated lysis (anti-CD2 plus anti-CD15) followed by overnight adherence to plastic. This procedure not only removes cell types reported to harbor SIV, but also enriches for progenitor cells. These cells were diluted in half-log steps and plated in 96-well plates (1000 to 3 cells/well, 60 replicates/dilution) in medium containing 30% FCS, 1% BSA and recombinant human growth factors in combination designed to drive colony growth toward the monocyte lineage (M-CSF plus GM-CSF). LDA, performed weekly from day 7 to 84, revealed that early during SIV infection (11-19 weeks), there was a significant increase in the number of functional progenitors in enriched BM. This was evidenced by 7-fold and 5-fold increases in total colony-forming cells (day 14 colonies) and in primative colony-forming cells (able to sustain longterm growth), respectively. Later in infection (weeks 31-40), the recovery of functional progenitors (early and long-term colony-forming cells) declined, dropping below preinfection values by approximately 42 weeks post infection. This drop occurred at times when no SIV could be detected (by syncytia formation, p27 ELISA, or in situ hybridization before or after coculture with CEM cells) in these lymphocyte/monocyte depleted samples. The monkeys were, however, antibody positive for SIV at all post-infection intervals, and the virus could be detected in whole BM and peripheral blood by coculture with PHA blasts or CEM cells. Interestingly, we have succeeded in isolating SIV from lymphocyte/monocyte depleted long term BM cultures in 5/5 animals evaluated at the latest time points (8-10 months) in this longitudinal study. Detection of virus by p27 ELISA required coculture with CEM cells and correlated with profound depression of stem cell function as measured in our long term assay system.
Keywords: Animal Antibodies, Viral/ANALYSIS *Blood Cell Count Bone Marrow/CYTOLOGY/IMMUNOLOGY/*MICROBIOLOGY Cell Division Cells, Cultured Cytopathogenic Effect, Viral Granulocyte-Macrophage Colony-Stimulating Factor/IMMUNOLOGY Longitudinal Studies Lymphocytes/MICROBIOLOGY Macaca mulatta Macrophage Colony-Stimulating Factor/IMMUNOLOGY Macrophages/MICROBIOLOGY Recombinant Proteins/PHARMACOLOGY Simian Acquired Immunodeficiency Syndrome/*IMMUNOLOGY Stem Cells/IMMUNOLOGY/*MICROBIOLOGY/PHYSIOLOGY SIV/IMMUNOLOGY/ISOLATION & PURIF Virus Cultivation ABSTRACT 910730
M9170972
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Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
