Human Herpesviruses‐6 and ‐7 (HHV‐6A, HHV‐6B and HHV‐7)

Abstract

Infection with human herpesviruses‐6 and ‐7 (HHV‐6/7) is universal in human populations. Early studies did not distinguish between the two virus species, HHV‐6A and HHV‐6B. No disease has been causally linked to HHV‐6A, but HHV‐6B and HHV‐7 are established as a cause of febrile illness in early childhood that is sometimes accompanied by fits. HHV‐6B can also cause encephalitis after haematopoietic stem cell transplant.

Chromosomally integrated HHV‐6 (either A or B) is a condition in which the complete viral genome is present in every nucleated cell in the body; it occurs in a minority of people and is vertically transmitted. Lack of recognition of this phenomenon has led to the misdiagnosis of active infection and inappropriate use of antiviral therapy. An important unresolved question is whether integrated virus is a cause of disease.

Key Concepts:

  • The term HHV‐6 covers two herpesvirus species, HHV‐6A and HHV‐6B.

  • HHV‐6A is not known to cause any disease.

  • HHV‐6B primary infection may cause fever, rash and febrile fits.

  • HHV‐6B reactivation may cause encephalitis in haematopoietic stem cell transplant recipients.

  • HHV‐7 primary infection may cause fever, rash and febrile fits.

  • Chromosomal integration of HHV‐6 (CIHHV‐6) involves either HHV‐6A or HHV‐6B and is always telomeric.

  • CIHHV‐6 occurs in approximately 1% of the human population and is vertically transmitted.

  • A lack of understanding of the phenomenon of CIHHV‐6 has led to misdiagnosis of disease and inappropriate antiviral treatment.

  • Whether or not CIHHV‐6 can reactivate in vivo and cause disease is currently unknown.

Keywords: HHV‐6A; HHV‐6B; CIHHV‐6; chromosomal integration; telomeres; encephalitis; febrile convulsions; febrile fits; status epilepticus

Figure 1.

Electron micrographs of HHV‐6 particles: (a) Negative contrast preparation showing three viruses that appear opaque and structureless because the virus envelope remained intact during preparation and was not penetrated by the contrast stain; three additional viruses (centre and below) have envelopes that were damaged during preparation, allowing the stain to enter and reveal the central icosahedral capsid (125 nm in diameter) within. The icosahedral capsids appear hexagonal in outline and short tubular capsomeres can be seen at their edges. (b) Ultrathin section through numerous enveloped viruses. The nucleic acid inner core is clearly visible within each capsid (diameter 125 nm), which is in turn surrounded by the dense tegument below the envelope with its viral glycoproteins.

Figure 2.

HHV‐6 cytopathic effect (CPE). Cultured peripheral blood lymphocytes showing the characteristic CPE induced by HHV‐6 infection: (a) Mock‐infected cells and (b) HHV‐6‐infected ballooning cells at the bottom of cell clump. Reproduced with permission from Di Luca et al. . © Elsevier.

Figure 3.

HHV‐6 and HHV‐7 antibodies in British children: (a) Prevalence of HHV‐6 IgG. Maternally acquired antibody dies away by approximately 26 weeks (6 months) after which natural primary infection begins, affecting all children by 104 weeks (2 years) and (b) comparison of HHV‐6 and HHV‐7 infection in British children in relation to age. Prevalence=number of cases with past infection/number with past infection plus uninfected ×100. Reproduced with permission from Ward . © Elsevier.

Figure 4.

HHV‐6 integration at the telomeric end of the short arm of chromosome 17 as mapped by FISH. Example of a dividing cell showing an HHV‐6 FISH green signal seen as two green dots at the tip of the short arm of one homologue of chromosome 17 demonstrating the location of the integrated virus on the sister chromatids. An arrow points to the other homologue of chromosome 17. The red signals are from locus‐specific probes for 9q34.3 (the telomeric region of the long arm) on both homologues of chromosome 9. Photomicrograph kindly supplied by Dr E Nacheva. Methods and materials used for FISH analysis were from Nacheva et al..

Figure 5.

Transmission of CIHHV‐6 from parent to child: pedigrees of four Japanese families. Individuals with CIHHV‐6 are shown in black, whereas those not so affected are shown in white. □, male; ○, female. Adapted with permission from Tanaka‐Taya et al..

Figure 6.

Virological features of primary HHV‐6 and HHV‐7 infections. Reproduced with permission from Ward . © Elsevier.

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Ward, Katherine N(May 2013) Human Herpesviruses‐6 and ‐7 (HHV‐6A, HHV‐6B and HHV‐7). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023616]