Megakaryocytopoiesis and granulopoiesis after murine cytomegalovirus infection.

Thrombopoiesis and granulopoiesis following murine cytomegalovirus infection were investigated by studying changes in megakaryocytes, megakaryocyte and granulocyte-macrophage progenitor cells, and spleen colony-forming cells. The soft gel in vitro culture system was used to assay for megakaryocyte and granulocyte-macrophage progenitor cells in marrow and spleen. Murine cytomegalovirus produced a mild thrombocytopenia to 90% of control values 1 day after infection at a time when marrow megakaryocyte levels were normal, suggesting a mild direct toxic effect of the virus on platelets. A reduction of megakaryocytes, megakaryocyte and granulocyte-macrophage progenitor cells, and spleen colony-forming cells to 40% to 60% of control values occurred within 24 to 48 hours of infection in association with an additional decrease in platelets to 58% of control levels on day 4. In vitro inoculation of marrow cell cultures with murine cytomegalovirus also resulted in a reduction of megakaryocyte- and granulocyte-macrophage colony-forming cells within 24 to 48 hours, suggesting that murine cytomegalovirus-induced thrombocytopenia and granulocytopenia may be in part caused by direct infection of precursor cells. The recovery of cells in the spleen was followed by a striking seven- to 10-fold increase in spleen colony-forming cells and megakaryocyte and granulocyte-macrophage progenitor cells in the spleen. These marked increases followed significant increases in spleen cell production of colony-stimulating activities within 2 days of murine cytomegalovirus infection, suggesting that hematopoietic cell recovery is mediated by increased local production of colony-stimulating activities in the spleen.