Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Viral Infections

Endothelial damage caused by cytomegalovirus and human herpesvirus-6

Bone Marrow Transplantation volume 31, pages 475–479 (2003)Cite this article

Summary:

Infection with cytomegalovirus (CMV) or human herpesvirus-6 (HHV-6) may have a role in vascular endothelial damage after bone marrow transplantation (BMT). In total, 41 patients who underwent BMT were classified into four groups (12, 10, 7, and 12 patients who were infected with both CMV and HHV-6, CMV alone, HHV-6, and neither virus, respectively). Levels of thrombomodulin, plasminogen activator inhibitor-1, and cyclic GMP were 7.5±1.7 FU/ml, 76.4±24.1 ng/ml, and 9.51±1.1 pmol/ml, respectively, in the patients with both viruses, while the respective values were 2.9±0.67 FU/ml, 33.8±8.09 ng/ml, and 2.90±1.4 pmol/ml in patients infected with CMV alone, 4.8±0.96 FU/ml, 47.7±9.21 ng/ml, and 5.48±0.55 pmol/ml in patients with HHV-6 alone, and 1.6±0.39, 17.5±7.88 ng/ml, and 0.45±0.3 in those with neither virus. All three markers were significantly higher in the three groups with at least one virus than in the uninfected patients (P<0.05), and were also higher in patients with HHV-6 alone than in those with CMV alone (P<0.05). These results suggest that infection by CMV or HHV-6 causes vascular endothelial injury, with HHV-6 having a stronger effect than CMV, and combined infection having a stronger effect than either virus alone. Such viral infection may be a cause of thrombotic microangiopathy after BMT.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Pettitt AR, Clark RE . Thrombotic microangiopathy following bone marrow transplantation. Bone Marrow Transplant 1994; 14: 495–504.

    CAS  PubMed  Google Scholar 

  2. Zeigler ZR, Shadduck RK, Nemunaitis J et al. Bone marrow transplant-associated thrombotic microangiopathy: a case series. Bone Marrow Transplant 1995; 15: 247–253.

    CAS  PubMed  Google Scholar 

  3. Schriber JR, Herzig GP . Transplantation-associated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Semin Hematol 1997; 34: 126–133.

    CAS  PubMed  Google Scholar 

  4. Kanamori H, Maruta A, Sasaki S et al. Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy. Bone Marrow Transplant 1998; 21: 705–709.

    Article  CAS  PubMed  Google Scholar 

  5. Holler E, Kolb HJ, Hiller E et al. Microangiopathy in patients on cyclosporine prophylaxis who developed acute graft-versus-host disease after HLA-identical bone marrow transplantation. Blood 1989; 73: 2018–2024.

    CAS  PubMed  Google Scholar 

  6. Tezcan H, Zimmer W, Fenstermaker R et al Severe cerebellar swelling and thrombotic thrombocytopenic purpura associated with FK506. Bone Marrow Transplant 1998; 21: 105–109.

    Article  CAS  PubMed  Google Scholar 

  7. Verburgh CA, Vermeij CG, Zijimans JM et al. Hemolytic syndrome following bone marrow transplantation. Case report and review of the literature. Nephrol Dial Transplant 1996; 11: 1332–1337.

    Article  CAS  PubMed  Google Scholar 

  8. Selby DM, Rudzki JR, Bayever ES et al. Vasculopathy of small muscular arteries in pediatric patients after bone marrow transplantation. Hum Pathol 1999; 30: 734–740.

    Article  CAS  PubMed  Google Scholar 

  9. Fawzi AA, Cunningham Jr ET . Central serous chorioretinopathy after bone marrow transplantation. Am J Ophthalmol 2001; 131: 804–805.

    Article  CAS  PubMed  Google Scholar 

  10. Fuge R, Bird JM, Fraser A et al. The clinical features, risk factors and outcome of thrombotic thrombocytopenic purpura occurring after bone marrow transplantation. Br J Haematol 2001; 113: 58–64.

    Article  CAS  PubMed  Google Scholar 

  11. Kim YG, Suga SI, Kang DH et al. Vascular endothelial growth factor accelerates renal recovery in experi-mental thrombotic microangiopathy. Kidney Int 2000; 58: 2390–2399.

    Article  CAS  PubMed  Google Scholar 

  12. Gimbrone Jr MA, Obin MS, Brock AF et al. Endothelial interleukin-8: a novel inhibitor of leukocyte–endothelial interactions. Science 1989; 246: 1601–1603.

    Article  CAS  PubMed  Google Scholar 

  13. Karakurum M, Shreeniwas R, Chen J et al. Hypoxic induction of interleukin-8 gene expression in human endothelial cells. J Clin Invest 1994; 93: 1564–1570.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chao NJ, Schmidt GM, Niland JC et al. Cyclosporin, methotrexate and prednisone compared with cyclosporin and prednisone for prophylaxis of acute graft-versus-host disease. N Engl J Med 1993; 329: 1225–1230.

    Article  CAS  PubMed  Google Scholar 

  15. Schmidt CA, Oettle H, Wilborn F et al. Demonstration of cytomegalovirus after bone marrow transplantation by polymerase chain reaction, virus culture and antigen detection in buffy coat leukocytes. Bone Marrow Transplant 1994; 13: 71–75.

    CAS  PubMed  Google Scholar 

  16. Takemoto T, Hashimoto T, Eizuru Y . Rapid diagnosis of CMV infection using the polymerase chain reaction. Isyoku 1992; 27: 745–751.

    Google Scholar 

  17. Yalcin S, Karpuzoglu T, Suleymanlar G . HHV-6 and HHV-7 infection in renal transplant recipients and healthy adults in Turkey. Arch Virol 1994; 136: 183–190.

    Article  CAS  PubMed  Google Scholar 

  18. Gondo H, Minematsu T, Harada M et al. Cytomegalovirus (CMV) antigenemia for rapid diagnosis and monitoring of CMV-associated disease after bone marrow transplantation. Br J Haematol 1994; 186: 130–137.

    Article  Google Scholar 

  19. Schmidt GM, Horak DM, Niland JC et al. A randomized controlled trial of prophylactic ganciclovir for cytome-galovirus pulmonary infection in recipients of allogeneic bone marrow transplants. N Engl J Med 1991; 324: 1005–1011.

    Article  CAS  PubMed  Google Scholar 

  20. Singhal S, Mehta J, Powles R et al. Three weeks of ganciclovir for cytomegaloviraemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1995; 15: 777–781.

    CAS  PubMed  Google Scholar 

  21. Nunberger W, Michelmann I, Burdach S et al. Endothelial dysfunction after bone marrow transplantation: increase of soluble thrombomodulin and PAI-1 in patients with multiple transplant-related complications. Ann Hematol 1998; 76: 61–65.

    Article  Google Scholar 

  22. Ormrod D, Scott LJ, Perry CM . Valaciclovir: a review of its long term utility in the management of genital herpes simplex virus and cytomegalovirus infections. Drugs 2000; 59: 839–863.

    Article  CAS  PubMed  Google Scholar 

  23. Jeejeebhoy FM, Zaltzman JS . Thrombotic microangiopathy in association with cytomegalovirus infection in a renal transplant patient: a new treatment strategy. Transplantation 1999; 68: 710–711.

    Article  Google Scholar 

  24. Matsuda Y, Hara J, Miyoshi H et al. Thrombotic microangiopathy associated with reactivation of human herpesvirus-6 following high-dose chemotherapy with autologous bone marrow transplantation in young children. Bone Marrow Transplant 1999; 24: 919–923.

    Article  CAS  PubMed  Google Scholar 

  25. Takatsuka H, Takamoto Y, Yamada S et al. Complications after bone marrow transplantation are manifestations of systemic inflammatory response syndrome. Bone Marrow Transplant 2000; 26: 419–426.

    Article  CAS  PubMed  Google Scholar 

  26. Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20: 864–874.

  27. Chen X, Christou NV . Relative contribution of endothelial cell and polymorphonuclear neutrophil activation in their interactions in systemic inflammatory response syndrome. Arch Surg 1996; 131: 1148–1154.

    Article  CAS  PubMed  Google Scholar 

  28. Takatsuka H, Takemoto Y, Yamada S et al. Cytokines and cytomegalo-virus disease following allogeneic bone marrow transplantation. Hematology 2001; 6: 271–278.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Ms R Tanaka for her expert technical assistance.

Author information

Authors and Affiliations

  1. Second Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

    H Takatsuka, T Wakae, A Mori, M Okada, Y Fujimori, Y Takemoto, T Okamoto & E Kakishita

  2. Third Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan

    A Kanamaru

Authors
  1. H Takatsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T Wakae
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Okada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y Fujimori
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y Takemoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Okamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Kanamaru
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E Kakishita
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takatsuka, H., Wakae, T., Mori, A. et al. Endothelial damage caused by cytomegalovirus and human herpesvirus-6. Bone Marrow Transplant 31, 475–479 (2003). https://doi.org/10.1038/sj.bmt.1703879

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703879

Keywords

This article is cited by

Search

Advanced search

Quick links