INFECTION AND REPLICATION OF HUMAN CYTOMEGALOVIRUS IN BONE-MARROW STROMAL CELLS - EFFECTS ON THE PRODUCTION OF IL-6, MIP-1-ALPHA, AND TGF-BETA(1)

We have investigated the mechanisms by which hematopoiesis is suppress ed in patients suffering from human cytomegalovirus (HCMV) infections, Mixed populations of human bone marrow stromal and hematopoietic prog enitor cells were inoculated with the Towne strain of HCMV to determin e whether these populations could be infected and support HCMV replica tion, We found that the Towne strain of HCMV was capable of infecting and replicating in a mixed population of bone marrow stromal cells, We observed no significant alterations in bone marrow stromal cell proli feration or the production of IL-6, GM-CSF, soluble c-kit ligand and T NF-alpha following HCMV replication in either stimulated lipopolysacch aride (LPS) or unstimulated conditions, In samples of culture supernat ants from LPS-stimulated HCMV-infected stromal cells, significant elev ations in MIP-1 alpha were observed, TGF-beta(1) levels on the other h and exhibited two patterns following HCMV exposure; either TGF-beta(1) levels decreased regardless of LPS stimulation or there was no effect , In addition, we observed that exposure to the Towne strain of HCMV r esulted in significant inhibition of both granulocytic and erythrocyti c colony formation in methylcellulose progenitor assays, Thus, both th e direct effect of HCMV on hematopoietic progenitors as well as altere d cytokine production by bone marrow stromal cells (including MIP-1 al pha and TGF-beta(1), but not IL-6) could contribute to hematopoietic f ailure during HCMV infection.