Fas-mediated apoptosis of hematopodetic progenitor cells in murine cytomegalovirus infected mice

Cytomegalovirus (CMV) has been shown to cause myelosuppression due to various mechanisms, direct effects on hematopoietic progenitor cells or alterations of stromal cell function. In the present study, we investigated the in vivo effects of tnurine CMV (MCMV) infection on hematopoietic progenitor cells. Inoculation of BALB/c mice with 1×10⁵ PFU (0.2LD50) of MCMV resulted in 44% reduction of bone marrow cellularity at day5 after infection (P<0.01), which recovered thereafter. Lineage marker negative. Sea-1 and c-kit positive (Lin-Sca-1⁺ c-kit⁺) fraction of bone marrow cells, shown to function as primitive hematopoietic progenitor cells, increased in number after infection with the highest level at day? (10 fold increase, A<0.01). In contrast, reduction of total number of colony-forming unit-spleen (CFU-S) was noted after infection, 51% of control (P< 0.01) at day 3, which recovered to the level higher than control at day?. Fas antigen expression in UirSca-1⁺ and Lin c-Jb'f fraction increased after infection with the highest level at day3. Cells undergoing apoptosis in Liir fraction increased at day3, from 0.10% in control to 1.49% (P< 0.01). These observations lead us to conclude that, although the phenotypically determined progenitor cells, Lin^-Sca- l+c-kit⁺ cells, increase in number as a host response to MCMV infection, their functional ability is impaired partially due to increased Fas expression and apoptosis.