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Published on: May 27, 2011
In vitro suppression of bone marrow progenitor cell differentiation by human herpesvirus 6 infection
1Department of Pathology, Medical College of Wisconsin, Milwaukee 53226.
Abstract:
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.
Insights
Human herpesvirus 6 (HHV-6) infection significantly impairs bone marrow function in transplant patients. Interferon-alpha neutralizing antibodies reversed these suppressive effects, suggesting a potential therapeutic target.
Area of Science:
- Hematology
- Virology
- Immunology
Background:
- Human herpesvirus 6 (HHV-6) infection is a serious complication in bone marrow transplant recipients.
- Marrow suppression is a critical consequence of HHV-6 infection, impacting patient outcomes.
Purpose of the Study:
- To investigate the in vitro effects of HHV-6 infection on normal bone marrow mononuclear cells.
- To assess the impact of HHV-6 on hematopoietic stem and progenitor cell differentiation and proliferation.
Main Methods:
- Infection of normal bone marrow mononuclear cells with HHV-6 in vitro.
- Methylcellulose-based colony formation assay to evaluate progenitor cell growth.
- Assessment of stromal layer outgrowth and viral presence in culture supernatants.
Main Results:
- Significant inhibition of colony-forming units of granulocyte and macrophage lineages (cfu-GM) by 43%.
- Marked reduction in granulocyte, erythrocyte, macrophage, and megakaryocyte lineages (cfu-GEMM) by 71%.
- Substantial decrease in erythroid burst-forming unit (bfu-E) by 73% and marrow stromal layer by 74%.
Conclusions:
- HHV-6 infection directly suppresses normal bone marrow hematopoietic progenitor cells and stromal cells in vitro.
- Interferon-alpha plays a crucial role in mediating the suppressive effects of HHV-6 on bone marrow.
- Neutralizing antibodies against interferon-alpha can reverse HHV-6-induced marrow suppression, indicating a potential therapeutic strategy.
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