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Human Herpesviruses: Human Herpesvirus 6

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Viral Infections of Humans

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Abstract

A snapshot of human herpesvirus 6 (HHV-6) reveals several key features of this virus that are clearly established. HHV-6 causes ubiquitous infection in infancy or early childhood that is typically a self-limited illness and generally associated with complete recovery. After primary infection, HHV-6 remains latent or persistent at several different sites, including the peripheral blood mononuclear cells, the salivary glands, female genital tract, liver, and central nervous system (CNS). Reactivation of HHV-6 occurs during periods of immune compromise and is associated with disease.

However, the biography of HHV-6 is rapidly evolving. Increasing interest and research have recently allowed a better understanding of the import and pathogenesis of HHV-6. Molecular techniques for the detection and determination of viral state have further defined the epidemiologic and clinical patterns of HHV-6 according to age, presence, and replicative state in different body sites and whether infection is new or reactivated. Taken together, these new findings have led to the classification of two variants, HHV-6A and HHV-6B, into distinct species.

Also of particular note is the unique ability of HHV-6 to integrate into human chromosomes. Human telomeres appear to be the consistent site of integration of the complete viral genome, which raises the possibility of disruption of the vital functions of the telomeres. In addition, the chromosomal integration of HHV-6 passed through the germline causes the great majority of congenital HHV-6 infections and can even cause disease upon reactivation later in life. Unknown, however, is the spectrum of pathogenic ramifications of the lifelong presence of virus, which is integrated in an individual’s chromosomes.

Other important areas that remain unresolved despite ongoing research include the definitive distinction between disease, which is due to the direct or indirect effects of HHV-6 infection versus when HHV-6 DNA is detected but unrelated to disease. The ubiquity of HHV-6 infections, its wide tropism, and its subsequent latency confound this distinction and indicate that currently the diagnosis of HHV-6 disease cannot be made on the basis of HHV-6 DNA detection alone.

Yet needed are not only clinically relevant diagnostic assays that are feasible and rapidly available but also effective prophylactic and therapeutic approaches for HHV-6 disease, especially among high-risk immunocompromised individuals. Although multiple antiviral agents have been shown in vitro to be active against HHV-6 infection, large controlled clinical trials have not been conducted. Most critical are efforts to increase recognition that understanding the immunopathogenesis of HHV-6 is important and that sufficient economic support is integral to this goal.

Caroline Breese Hall died before publication of this work was completed.

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Authors and Affiliations

  1. Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Brenda L. Tesini

  2. Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Brenda L. Tesini & Mary T. Caserta

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  1. Brenda L. Tesini
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Correspondence to Brenda L. Tesini .

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Editors and Affiliations

  1. School of Public Health, Yale University, Washington, DC, USA

    Richard A. Kaslow

  2. Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA

    Lawrence R. Stanberry

  3. Cters for Disease Control and Prevention, National Center for Emerging and Zoonoti, Fort Collins, CO, USA

    Ann M. Powers

Section Editor information

  1. Departmant of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York, USA

    Lawrence R. Stanberry

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Tesini, B.L., Caserta, M.T. (2023). Human Herpesviruses: Human Herpesvirus 6. In: Kaslow, R.A., Stanberry, L.R., Powers, A.M. (eds) Viral Infections of Humans. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-9544-8_37-1

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