Summary
Cytomegalovirus (CMV) recurrence from latency is a major risk factor in bone marrow transplantation (BMT). Owing to the immunodepletive treatment, ablation of the immune control of latent CMV is responsible for recurrence and cytopathogenic spread of the virus in vital tissues. There is increasing evidence for reconstituting bone marrow being itself a target tissue of CMV. By inhibiting post-transplantation hematopoiesis, CMV is causal for maintenance of the immunocompromised state, which leads to a prolonged phase of persistent virus replication. Based on results in a murine model of BMT and concurrent CMV infection, we discuss possible mechanisms of CMV-mediated bone marrow graft failure. It is concluded that an irremediable damage of bone marrow stroma by CMV is responsible for a reduced rate of regeneration of the marrow-repopulating, pluripotent stem cell.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Apperley JF, Dowding C, Hibbin J, Buiter J, Matutes E, Sissons PJ, Gordon M, Goldman JM (1989) The effect of cytomegalovirus on hemopoiesis: in vitro evidence for selective infection of marrow stromal cells. Exp Hematol 17: 38–45
Busch FW, Mutter W, Koszinowski UH, Reddehase MJ (1991) Rescue of myeloid lineage-committed preprogenitor cells from cytomegalovirus-infected bone marrow stroma. J Virol 65: 981–984
Forman SJ (1991) Bone marrow transplantation. Transplant Proc 23 [Suppl 3]: 110–114
Ho M (1991) Observations from transplantation contributing to the understanding of pathogenesis of CMV infection. Transplant Proc 23 [Suppl 3]: 104–109
Jones RJ, Wagner JE, Celano P, Zicha MS, Sharkis SJ (1990) Separation of pluripotent hematopoietic stem cells from spleen colony-forming cells. Nature 347: 188–189
Koszinowski UH, Del Val M, Reddehase MJ (1990) Cellular and molecular basis of the protective immune response to cytomegalovirus infection. Curr Top Microbiol Immunol 154: 189–220
Meyers JD, Flournoy N, Thomas ED (1986) Risk factors for cytomegalovirus infection after human bone marrow transplantation. J Infect Dis 153: 478–488
Mutter W, Reddehase MJ, Busch FW, Bühring H-J, Koszinowski UH (1988) Failure in generating hemopoietic stem cells is the primary cause of death from cytomegalovirus disease in the immunocompromised host. J Exp Med 167: 1645–1658
Paulin T, Ringden O, Lonnquist B (1985) Faster immunological recovery after bone marrow transplantation in patients without cytomegalovirus infection. Transplantation 39: 377–384
Philipps RA (1985) Comparison of different assays for multipotent hematopoietic stem cells. In: Ford RJ, Maizel AL (eds) Mediators in cell growth and differentiation. Raven, New York, pp 135–145
Quesenberry PJ (1989) Stromal cells in long-term bone marrow cultures. In: Tavassoli M (ed) Handbook of the hemopoietic microenvironment. Humana, Clifton, NJ, pp 253–285
Reddehase MJ (1991) Bone marrow dysfunction in irradiated, cytomegalovirus-infected mice. Transplant Proc 23 [Suppl 3]: 8–11
Simmons P, Kaushansky K, Torok-Storb B (1990) Mechanisms of cytomegalovirus-mediated myelosuppression: perturbation of stromal cell function versus direct infection of myeloid cells. Proc Natl Acad Sci USA 87: 1386–1390
Witte ON (1990) Steel locus defines new multipotent growth factor. Cell 63: 5–6
Author information
Authors and Affiliations
Additional information
This work was supported by theDeutsche Forschungsgemeinschaft, Sonderforschungsbereich 322, project C4 (Hematopoiesis and Virus Infection).
Rights and permissions
About this article
Cite this article
Reddehase, M.J., Dreher-Stumpp, L., Angele, P. et al. Hematopoietic stem cell deficiency resulting from cytomegalovirus infection of bone marrow stroma. Ann Hematol 64 (Suppl 1), A125–A127 (1992). https://doi.org/10.1007/BF01715364
Issue Date:
DOI: https://doi.org/10.1007/BF01715364