Analysis of hematopoietic stem and progenitor cell populations in
cytomegalovirus-infected mice
AE Gibbons, P Price and GR Shellam
Department of Microbiology, University of Western Australia, Queen
Elizabeth II Medical Centre, Nedlands.
We have studied the effects of murine cytomegalovirus (MCMV) infection on
bone marrow stem and progenitor cell populations to find an explanation for
the defects in hematopoiesis that accompany CMV infections in patients.
Sublethal MCMV infection of BALB/c mice resulted in a 5- to 10-fold
decrease in the numbers of myeloid (colony- forming
unit-granulocyte-macrophage [CFU-GM]) and erythroid (burst- forming
unit-erythroid [BFU-E]) progenitor cells in the marrow, but not in
primitive myeloerythroid progenitor cell (colony-forming unit-spleen
[CFU-S]) numbers. In contrast, we observed a 10- to 20-fold reduction in
CFU-S as well as CFU-GM and BFU-E in lethally infected mice. Depletion of
marrow CFU-GM was less severe in C57BL/10 and C3H/HeJ mice, which are more
resistant to the effects of MCMV infection. Treatment of bone marrow cells
with MCMV preparations in vitro did not reduce the numbers of CFU-GM,
although up to 10% of the cells were productively infected. This finding
suggests that CFU-GM were not susceptible to lytic MCMV infection in vitro
and are probably not eliminated by lytic infection in vivo. Increases in
the frequencies of Sca-1+Lin- marrow cells, a population that includes
cells with the characteristics of pluripotential stem cells, were observed
in MCMV- infected BALB/c, C57BL/10, and DBA/2J mice. Increases in the
frequencies of c-kit+Lin- marrow cells were only seen in DBA/2J mice. MCMV
infection did not impair the function of pluripotential stem cells because
transplantation of marrow from MCMV-infected donors into irradiated
recipient mice resulted in successful reconstitution of the T, B, and
myeloid cell lineages.
Volume 86,
Issue 2,
pp. 473-481,
07/15/1995
Copyright © 1995 by The American Society of Hematology
