Article

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).

Center for Comparative Medicine, University of California, Davis, California, USA.
Comparative medicine (impact factor: 1.05). 01/2012; 62(1):61-8. pp.61-8
Source: PubMed

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.

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Keywords

Asian monkeys
 
cell-cell contact
 
contact time
 
detectable SRV-infection
 
direct effects
 
granulocyte-macrophage colony formation
 
hematopoietic progenitor
 
hematopoietic progenitor cell differentiation
 
Peripheral blood cytopenias
 
progenitor cell populations
 
reverse transcriptase assay
 
rhesus macaque bone marrow
 
secondary effects
 
simian betaretrovirus infection
 
SRV infection
 
SRV-exposed progenitor-associated stroma
 
SRV-infected stromal cells
 
statistically significant reduction
 
supportive bone marrow stroma
 
viral infection