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:

Allografting

Transmission of integrated human herpesvirus-6 in allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 40, pages 563–566 (2007)Cite this article

Abstract

Human herpesvirus 6 (HHV-6) viremia, as detected by polymerase chain amplification, occurs in approximately half of allogeneic hematopoietic stem cell transplant recipients. The significance of such viremia is incompletely understood, but HHV-6 encephalitis and bone marrow suppression are increasingly being recognized in patients with high viral DNA. We report two patients in whom donor-to-recipient transmission occurred through hematopoietic transplant by means of chromosomally integrated (CI) HHV-6. Iatrogenic transmission manifested at engraftment as asymptomatic elevation of HHV-6 viral DNA of 3600 and 15 400 DNA copies/ml in plasma and 6.1 × 106 and 9.7 × 105 DNA copies/ml in the whole blood. Both donors had elevated plasma HHV-6 PCR at 5.6 × 104 and 1.3 × 105 DNA copies/ml and strikingly elevated whole blood HHV-6 levels at 4.1 × 106 and 4.7 × 106 DNA copies/ml, respectively. CI of the virus was traced to the mother of one patient and his donor. CI of HHV-6 may confound the interpretation of HHV-6 viremia after stem cell transplantation; consideration of the possibility of CI HHV-6 will avoid unnecessary antiviral therapy.

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

Similar content being viewed by others

References

  1. Zerr DM, Meier AS, Selke SS, Frenkel LM, Huang ML, Wald A et al. A population-based study of primary human herpesvirus 6 infection. N Engl J Med 2005; 352: 768–776.

    Article  CAS  PubMed  Google Scholar 

  2. Zerr DM, Corey L, Kim HW, Huang ML, Nguy L, Boeckh M . Clinical outcomes of human herpesvirus 6 reactivation after hematopoietic stem cell transplantation. Clin Infect Dis 2005; 40: 932–940.

    Article  PubMed  Google Scholar 

  3. Clark DA, Nacheva EP, Leong HN, Brazma D, Li YT, Tsao EH et al. Transmission of integrated human herpesvirus 6 through stem cell transplantation: implications for laboratory diagnosis. J Infect Dis 2006; 193: 912–916.

    Article  PubMed  Google Scholar 

  4. Boutolleau D, Agut H, Gautheret-Dejean A . Human Herpes 6 Genome Integration: a possible cause of misdiagnosis of active viral infection? J Infect Dis 2006; 194: 1019–1020.

    Article  PubMed  Google Scholar 

  5. Ward KN, Leong HN, Nacheva EP, Howard J, Atkinson CE, Davies NW et al. Human herpesvirus 6 chromosomal integration in immunocompetent patients results in high levels of viral DNA in blood, sera, and hair follicles. J Clin Microbiol 2006; 44: 1571–1574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ward KN, Leong HN, Thiruchelvam AD, Atkinson CE, Clark DA . HHV-6 DNA level in CSF due to primary infection differs from that in chromosomal viral integration and has implications for the diagnosis of encephalitis. J Clin Microbiol 2007; 45: 1298–1304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Leong HN, Tuke PW, Tedder RS, Khanom AB, Eglin RP, Atkinson CE et al. The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J Med Virol 2007; 79: 45–51.

    Article  CAS  PubMed  Google Scholar 

  8. Tanaka-Taya K, Sashihara J, Kurahashi H, Amo K, Miyagawa H, Kondo K et al. Human herpesvirus 6 (HHV-6) is transmitted from parent to child in an integrated form and characterization of cases with chromosomally integrated HHV-6 DNA. J Med Virol 2004; 73: 465–473.

    Article  PubMed  Google Scholar 

  9. Tsao E, Clark DA, Tsao EHF, Leong HN, Ward KN, Nacheva EP et al. integration of human herpesvirus 6 (correspondence). J Infect Dis 2006; 194: 1021–1023.

    Article  Google Scholar 

  10. Bandobashi K, Daibata M, Kamioka M, Tanaka Y, Kubonishi I, Taguchi H et al. Human herpesvirus 6 (HHV-6)-positive Burkitt's lymphoma: establishment of a novel cell line infected with HHV-6. Blood 1997; 90: 1200–1207.

    CAS  PubMed  Google Scholar 

  11. Daibata M, Taguchi T, Nemoto Y, Taguchi H, Miyoshi I . Inheritance of chromosomally integrated human herpesvirus 6 DNA. Blood 1999; 94: 1545–1549.

    CAS  PubMed  Google Scholar 

  12. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  13. Dahl H, Linde A, Sundqvist VA, Wahren B . An enzyme-linked immunosorbent assay for IgG antibodies to human herpes virus 6. J Virol Methods 1990; 29: 313–323.

    Article  CAS  PubMed  Google Scholar 

  14. Reddy S, Manna P . Quantitative detection and differentiation of human herpesvirus 6 subtypes in bone marrow transplant patients by using a single real-time polymerase chain reaction assay. Biol Blood Marrow Transplant 2005; 11: 530–541.

    Article  CAS  PubMed  Google Scholar 

  15. Lo YM, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998; 62: 768–775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ogata M, Kikuchi H, Satou T, Kawano R, Ikewaki J, Kohno K et al. Human herpesvirus 6 DNA in plasma after allogeneic stem cell transplantation: incidence and clinical significance. J Infect Dis 2006; 193: 68–79.

    Article  CAS  PubMed  Google Scholar 

  17. Hentrich M, Oruzio D, Jager G, Schlemmer M, Schleuning M, Schiel X et al. Impact of human herpesvirus-6 after haematopoietic stem cell transplantation. Br J Haematol 2005; 128: 66–72.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital, Houston, TX, USA

    R T Kamble, H E Heslop, M K Brenner & G Carrum

  2. Department of Virology, Barts and The London NHS Trust, London, UK

    D A Clark

  3. Division of Infection and Immunity, Centre for Virology, Royal Free and University College Medical School, London, UK

    H N Leong

Authors
  1. R T Kamble
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D A Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H N Leong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H E Heslop
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M K Brenner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G Carrum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R T Kamble.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kamble, R., Clark, D., Leong, H. et al. Transmission of integrated human herpesvirus-6 in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 40, 563–566 (2007). https://doi.org/10.1038/sj.bmt.1705780

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705780

Keywords

This article is cited by

Search

Advanced search

Quick links