Inhibitory Effects of Beta-herpesviruses on Hematopoiesis

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Human herpesvirus 6 (HHV-6), as well as human cytomegalovirus, is related to various severe complications after hematopoietic stem cell transplantation (SCT) under extensive use of immunosuppressive drugs. We monitored the activity of five herpesviruses including three beta-herpesviruses after allogeneic SCT, and showed that HHV-6 is associated with delayed engraftment of hematopoietic cells after SCT. In vitro models, however, have not proven the relationship between beta-herpesviruses and the clinical manifestations.We established the in vitro systems to assess the effects of HHV-6 and related beta herpesviruses on hematopoietic colony formation. We comparatively examined HHV-6A, HHV6B, and human herpesvirus 7 (HHV-7). We showed that both type of HHV-6 suppresses all three lineages of hematopoietic colony formation of erythroid (BFU-E), granulocyte /macrophage (CFU-GM), and megakaryocyte (CFU-Meg) in vitro. On the other hand, HHV-7 did not have any suppressive effect on in vitro hema … More topoietic colony formation..We focused on HHV-6B and further examined the interaction with human CD34+ cells, which are a major source of hematopoietic progenitor cells. CD34+ cells were immunomagnetically isolated from cord blood mononuclear cells using anti-CD34+ antibodies coated onto either Dynabeads or MACS beads. The CD34+ population selected with Dynabeads showed a broad range of fluorescence. The population selected with MACS beads showed a narrow range of fluorescence. After infection with HHV-6, Two transcripts of the immediate early genes were detected with both cell populations. HHV-6 suppressed colony formation of BFU-E, CFU-GM, and CFU-Meg. HHV-6 suppressed cell growth after 3 to 7 days culture in the presence of thrombopoietin (TPO). More differentiated CD34+ cells were more susceptible to the effects of HHV-6. These data indicate that the targets for hematopoietic suppression by HHV-6 are relatively differentiated cells that express a lower amount of the CD34 antigen (dim cells) among a heterogeneous cell population. Less