In vitro 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.
Knox
K K
KK
Department of Pathology, Medical College of Wisconsin, Milwaukee 53226.
Carrigan
D R
DR
D001853:Bone Marrow / Q000382:microbiology* / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005455:Fluorescent Antibody Technique; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D013234:Stem Cells / Q000382:microbiology* / Q000473:pathology