INVITRO SUPPRESSION OF BONE-MARROW PROGENITOR-CELL DIFFERENTIATION BY HUMAN HERPESVIRUS-6 INFECTION

Suppression of marrow function may be one of the most serious effects of human herpesvirus 6 (HHV-6) infection in marrow transplant patients. In this study, normal bone marrow mononuclear cells were infected in vitro with HHV-6, and a methylcellulose-based colony formation assay was used to evaluate the impact of the infection on marrow cell differentiation and proliferation. Results demonstrated that the outgrowth of colony-forming units of granulocyte and macrophage lineages (cfu-GM) was decreased by approximately 43%, that growth of cfu of granulocyte, erythrocyte, macrophage, and megakaryocyte lineages (cfu-GEMM) was inhibited by an average of 71%, and that the erythroid burst-forming unit (bfu-E) was decreased by approximately 73%. Further, outgrowth of the marrow stromal layer was reduced 74%. Direct infection of bone marrow monocytes was observed, although cell-free virus could not be detected in infected culture supernatants. Addition of a neutralizing monoclonal antibody specific for interferon-alpha to the infected cultures resulted in an almost complete reversal of the viral suppressive effects.