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Human Herpesviruses 6A, 6B, and 7

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  • Authors: Henri Agut1, Pascale Bonnafous4, Agnès Gautheret-Dejean6
  • Editors: Randall T. Hayden10, Donna M. Wolk11, Karen C. Carroll12, Yi-Wei Tang13
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Sorbonne Universités, UPMC, CIMI-Paris UMRS CR7, PVI Team, Paris, France; 2: INSERM, CIMI-Paris U1135, PVI Team, Paris, France; 3: AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Service de Virologie, Paris, France; 4: Sorbonne Universités, UPMC, CIMI-Paris UMRS CR7, PVI Team, Paris, France; 5: INSERM, CIMI-Paris U1135, PVI Team, Paris, France; 6: Sorbonne Universités, UPMC, CIMI-Paris UMRS CR7, PVI Team, Paris, France; 7: INSERM, CIMI-Paris U1135, PVI Team, Paris, France; 8: AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Service de Virologie, Paris, France; 9: Université René Descartes, Faculté de Pharmacie, Laboratoire de Microbiologie UPRES EA 4065, Paris, France; 10: Clinical and Molecular Microbiology, Department of Pathology, St. Jude’s Children’s Research Hospital, Memphis, TN; 11: Geisinger Clinic, Department of Laboratory Medicine, Danville, PA; 12: Johns Hopkins University Hospital, Baltimore, MD; 13: Clinical Microbiology Service, Memorial Sloane-Kettering Institute, New York, NY
  • Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0007-2015
  • Received 15 March 2015 Accepted 15 June 2015 Published 17 June 2016
  • Henri Agut, henri.agut@aphp.fr
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  • Abstract:

    Human roseoloviruses include three different species, human herpesviruses 6A, 6B, and 7 (HHV-6A, HHV-6B, HHV-7), genetically related to human cytomegalovirus. They exhibit a wide cell tropism and, like other herpesviruses, induce a lifelong latent infection in humans. In about 1% of the general population, HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6). Many active infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. They also may cause serious diseases, particularly in immunocompromised individuals, including hematopoietic stem-cell transplant (HSCT) and solid-organ transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients. This opportunistic pathogenic role is formally established for HHV-6 infection and less clear for HHV-7. It mainly concerns the central-nervous system, bone marrow, lungs, gastrointestinal tract, skin, and liver. As the best example, HHV-6 causes both exanthema subitum, a benign disease associated with primary infection, and severe encephalitis associated with virus reactivations in HSCT recipients. Diagnosis using serologic and direct antigen-detection methods currently exhibits limitations. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time polymerase-chain reaction (PCR). The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active infections, but there is currently no consensus regarding the indications of treatment or specifics of drug administration. Numerous questions about HHV-6A, HHV-6B, HHV-7 are still pending, concerning in particular clinical impact and therapeutic options in immunocompromised patients.

  • Citation: Agut H, Bonnafous P, Gautheret-Dejean A. 2016. Human Herpesviruses 6A, 6B, and 7. Microbiol Spectrum 4(3):DMIH2-0007-2015. doi:10.1128/microbiolspec.DMIH2-0007-2015.

Key Concept Ranking

Linear Double-Stranded DNA
0.4460266
Human herpesvirus 6
0.42211717
Acquired Immunodeficiency Syndrome
0.40713847
0.4460266

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/content/journal/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015
2016-06-17
2017-06-26

Abstract:

Human roseoloviruses include three different species, human herpesviruses 6A, 6B, and 7 (HHV-6A, HHV-6B, HHV-7), genetically related to human cytomegalovirus. They exhibit a wide cell tropism and, like other herpesviruses, induce a lifelong latent infection in humans. In about 1% of the general population, HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6). Many active infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. They also may cause serious diseases, particularly in immunocompromised individuals, including hematopoietic stem-cell transplant (HSCT) and solid-organ transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients. This opportunistic pathogenic role is formally established for HHV-6 infection and less clear for HHV-7. It mainly concerns the central-nervous system, bone marrow, lungs, gastrointestinal tract, skin, and liver. As the best example, HHV-6 causes both exanthema subitum, a benign disease associated with primary infection, and severe encephalitis associated with virus reactivations in HSCT recipients. Diagnosis using serologic and direct antigen-detection methods currently exhibits limitations. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time polymerase-chain reaction (PCR). The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active infections, but there is currently no consensus regarding the indications of treatment or specifics of drug administration. Numerous questions about HHV-6A, HHV-6B, HHV-7 are still pending, concerning in particular clinical impact and therapeutic options in immunocompromised patients.

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FIGURE 1

Proposal of algorithm for the diagnosis and therapy monitoring of HHV-6-associated disease in an immunocompromised patient. It must be recalled that some of the virological tests mentioned in this algorithm are not widely available in medical centers and that the predictive value of positive results for the diagnosis of infection or disease is not formally established for many of the indicated sample types.

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0007-2015
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TABLE 1

Clinical syndromes associated with HHV-6 infections

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0007-2015
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TABLE 2

Diagnostic approaches for HHV-6 and HHV-7 infections

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0007-2015

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