THE SUPPRESSIVE EFFECT OF CYTOMEGALOVIRUS ON BONE-MARROW - A MURINE MODEL

Cytomegalovirus infection causes significant morbidity and mortality in patients who undergo bone marrow transplantation and in patients with AIDS. We studied the effect of murine cytomegalovirus on murine bone marrow cells stimulated with purified recombinant macrophage and granulocyte-macrophage colony-stimulating factors (M-CSF and GM-CSF). In a clonogenic soft agar assay, M-CSF and GM-CSF colony-forming units were reduced in a viral dose-dependent fashion. Bone marrow cells from acutely infected mice were similarly affected, but those from latently infected mice responded normally. Infection of bone marrow cells occurred as measured by in situ hybridization and polymerase chain reaction. After infection, specific binding of M-CSF by infected bone marrow cells was lower than that by control cells. We conclude that CMV suppresses hematopoiesis and that this suppression is at least partially mediated by alteration of M-CSF binding on bone marrow cells.