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Human herpesvirus 6 infection in hematopoietic cell transplant recipients

Author
Danielle Zerr, MD, MPH
Section Editors
Martin S Hirsch, MD
Michael Boeckh, MD
Deputy Editor
Anna R Thorner, MD

INTRODUCTION

Human herpesvirus 6 (HHV-6) is a member of the Roseolovirus genus of the beta-herpesvirus subfamily of human herpesviruses. There are two HHV-6 variants, HHV-6A and HHV-6B. Based on their distinctive biological properties and genome sequences, the Herpesvirales Study Group of the International Committee on Taxonomy of Viruses has classified HHV-6A and HHV-6B as two distinct herpesvirus species [1].

The epidemiology, clinical manifestations, diagnosis, and treatment of HHV-6 infections in hematopoietic cell transplant (HCT) recipients will be discussed here. HHV-6 infections in patients who are not HCT recipients are presented separately. (See "Virology, pathogenesis, and epidemiology of human herpesvirus 6 infection" and "Human herpesvirus 6 infection in children: Clinical manifestations; diagnosis; and treatment" and "Clinical manifestations, diagnosis, and treatment of human herpesvirus 6 infection in adults".)

EPIDEMIOLOGY

The vast majority of documented primary infections and reactivation events are due to human herpesvirus (HHV)-6B. HHV-6B infects most children within the first three years of life and, like other herpesviruses, it establishes latency after primary infection. HHV-6B may reactivate in immunocompromised hosts, especially following allogeneic hematopoietic cell transplantation (HCT). Encephalitis is the most clearly established clinical manifestation of HHV-6 reactivation in allogeneic HCT recipients and may result in substantial morbidity. Little is known about the epidemiology or clinical implications of HHV-6A.

The ubiquitous nature of HHV-6B and the fact that it causes latent infection complicate the ability to link disease with the virus. Further complicating this situation is the condition of inherited chromosomally integrated HHV-6, an emerging aspect of HHV-6 biology that has not been studied adequately [2]. Inherited chromosomally integrated HHV-6 occurs when HHV-6A or HHV-6B integrates into germ-line cells, resulting in vertical transmission of chromosomally integrated HHV-6 [3]. Affected individuals have the HHV-6 genome integrated into a chromosome in every nucleated cell of their body, resulting in high levels of viral DNA in the blood and tissues in the absence of reactivation. Inherited chromosomally integrated HHV-6 is found in 1 to 2 percent of the population. Its impact on HCT outcomes is unknown; at the very least, it may cause concern and confusion among clinicians when high viral levels are detected. (See 'Detecting inherited chromosomal integration' below.)

HHV-6B reactivation occurs in 30 to 70 percent of patients undergoing allogeneic HCT [4-8], with encephalitis occurring in only a small subset of these patients. HHV-6 reactivation often manifests as HHV-6 viremia and typically occurs between two and four weeks after transplantation. HHV-6B accounts for most reactivations, with HHV-6A accounting for fewer than 3 percent of cases [6,9,10]. It seems likely that previously reported cases in which HHV-6A was detected may actually represent inherited chromosomally integrated HHV-6. (See 'Detecting inherited chromosomal integration' below.)

                                  

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Literature review current through: Nov 2016. | This topic last updated: Mon Jun 01 00:00:00 GMT+00:00 2015.
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