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Virology, pathogenesis, and epidemiology of human herpesvirus 6 infection

Cécile Tremblay, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Anna R Thorner, MD


Human herpesvirus 6 (HHV-6) was first isolated and characterized from patients with lymphoproliferative disorders [1] and was originally named human B-lymphotropic virus. Its name was changed to human herpesvirus 6 as its tropism was further characterized [2].

The virology, pathogenesis, and epidemiology of HHV-6 infection will be discussed here. The clinical manifestations, diagnosis, and treatment in adults and children are presented separately; HHV-6 infection in hematopoietic cell transplant recipients is also discussed elsewhere. (See "Clinical manifestations, diagnosis, and treatment of human herpesvirus 6 infection in adults" and "Human herpesvirus 6 infection in children: Clinical manifestations; diagnosis; and treatment" and "Human herpesvirus 6 infection in hematopoietic cell transplant recipients".)


HHV-6 is a member of the Herpesviridae family. Its genetic and biologic similarities to human cytomegalovirus (CMV) have prompted its classification in the beta herpesvirus subfamily (genus Roseolovirus, along with human herpesvirus 7 [HHV-7]) [3]. There are two HHV-6 variants, HHV-6A and HHV-6B. Based on their distinctive biological properties and genome sequences, HHV-6A and HHV-6B are classified as two distinct herpesvirus species [4]. HHV-6A and HHV-6B also differ in epidemiology, growth properties, antigenic properties, and restriction endonuclease profiles [5-8]. The nucleotide sequence identity between the two variants ranges from 75 to 95 percent depending upon which gene is compared.


As with other herpes viruses, mature HHV-6 virions are double-stranded DNA viruses, approximately 200 nm in diameter and are composed of four main structural elements: an electron-dense core, a capsid with icosahedral symmetry, a tegument, and an outer envelope.

Cell tropism — HHV-6 replicates most efficiently in vitro in activated primary T cells as well as in continuous T cell lines. However, the virus can also replicate with varying efficiency in a wide array of host cell types including monocytes/macrophages, natural killer cells, astrocytes, megakaryocytes, and glial cell lineages [2,9-12]. HHV-6 can also be recovered in vivo from a broad range of tissues such as lymph nodes, peripheral blood mononuclear cells (PBMCs), renal tubular cells, salivary glands, and the central nervous system [13-19]. HHV-6 has also been identified in astrocytes from gliomas, suggesting a potential role in tumorigenesis [20,21].


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Literature review current through: Sep 2016. | This topic last updated: Jul 7, 2015.
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