title: Effects of simian betaretrovirus serotype 1 (SRV1) infection on the differentiation of hematopoietic progenitor cells (CD34+) derived from bone marrow of rhesus macaques (Macaca mulatta).
abstract: Peripheral blood cytopenias, particularly persistent anemia and neutropenia, are commonly associated with simian betaretrovirus infection of Asian monkeys of the genus Macaca. The pathogenetic mechanisms underlying these hematologic abnormalities are not well understood. The  current study investigated the in vitro tropism of simian betaretrovirus (SRV) for both hematopoietic progenitor (CD34(+)) and stromal cells obtained from rhesus macaque bone marrow and assessed the effects of infection on hematopoietic progenitor cell differentiation in vitro. After  in vitro exposure, SRV proviral DNA could be demonstrated by real-time PCR in cells and the reverse transcriptase assay in supernatants from SRV-exposed progenitor-associated stroma, but not in differentiated colonies derived from SRV-exposed progenitors. Furthermore, in vitro exposure involving  cell-cell contact of uninfected CD34(+) progenitor cells with SRV-infected stromal cells resulted in a statistically significant reduction in granulocyte-macrophage colony formation in absence of detectable SRV-infection of progenitor cells. Reduction in colony formation  occurred in a 'dose-dependent' fashion with increasing contact time. No effects on erythroid lineages and RBC differentiation were noted. Our results suggest that hematologic abnormalities observed during SRV disease (natural or experimental) of rhesus macaques may not result from direct effects  of viral infection of progenitor cell populations, but rather be (at least in part) a consequence of SRV infection of supportive bone marrow stroma with secondary effects on differentiation of associated progenitor cells.
authors.affiliation: Center for Comparative Medicine, University of California, Davis, California, USA. nestor.montiel@ars.usda.gov
authors.forename: Nestor A
authors.initials: NA
authors.lastname: Montiel
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Todd
authors.forename: JoAnn
authors.initials: J
authors.lastname: Yee
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lerche
mesh_terms: D000818:Animals; D000830:Animals, Laboratory; D018952:Antigens, CD34 / Q000378:metabolism; D030121:Betaretrovirus; D002454:Cell Differentiation / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology* / Q000821:virology; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008992:Monkey Diseases / Q000503:physiopathology* / Q000821:virology*; D023461:Myeloid Progenitor Cells; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D012192:Retroviridae Infections / Q000503:physiopathology / Q000662:veterinary*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D017154:Stromal Cells / Q000821:virology
chemical_list: D018952:Antigens, CD34