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Human herpesvirus 6 (HHV-6) was isolated in tissue culture in
1986 from peripheral blood leukocytes of patients with both lymphoproliferative
disorders and HIV infection. It is the major etiologic agent of
exanthem subitum and has also been implicated in other clinical
syndromes. HHV-6 is a prototypical member of the betaherpesvirus family
of herpesviruses, which also includes human herpesvirus 7 (HHV-7)
and human cytomegalovirus (HCMV). The virus has a double- stranded
DNA genome contained within an icosahedral capsid, surrounded by
an outer envelope. HHV-6 is subclassified as either variant A or
B, based on differences in nucleotide sequence, restriction enzyme
profile, and reactivity with monoclonal antibodies. HHV-6B is the
subtype associated with exanthem subitum.1 In
contrast to the other human herpesviruses, which are maintained
in a latent state in the host cell as circularized genomes.
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Infection with human herpesvirus 6 (HHV-6) is ubiquitous, and
virtually all children are infected by 2 to 3 years of age. Infection
is seldom seen before 6 months of age, presumably due to the protective
effect of transplacental antibody. The incidence of infection peaks
between 6 and 12 months of age. HHV-6 can be found in the salivary
gland, and is shed in saliva of seropositive individuals, suggesting that
saliva is the probable route of acquisition of infection. Primary
infection in children most likely occurs via contact with HHV-6 shed
in the secretions of older children or caregivers. HHV-6 can also
be associated with congenital infections, which may occur through
transmission of chromosomally integrated viral DNA in germ line
cells: the clinical significance of such infections is not known.2,3
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HHV-6 is a prototypical member of the betaherpesvirus family
of herpesviruses, which also includes human herpesvirus 7 (HHV-7)
and human cytomegalovirus (HCMV). It has tropism for T cells, and
molecular studies reveal homology with HCMV, suggesting that the
virus belongs to the family Herpesviridae. More
recent evidence suggests that HHV-6 can be maintained in the host
cell in a chromosomally integrated form, capable of producing viral mRNA
and protein and, presumably, infectious virus.2
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Clinical Manifestations
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The spectrum of disease associated with primary human herpesvirus
6 (HHV-6) infection is broad, ranging from asymptomatic infection to
fatal disseminated disease. Most commonly, however, primary infection
occurs early in life and is manifest as either exanthem
subitum or an undifferentiated febrile illness. Reports of
HHV-6 infection linked to other clinical syndromes must be interpreted
cautiously. Because infection is ubiquitous and persistent in nature,
the finding of HHV-6 antibody, or even isolation of the virus, cannot
with certainty always document HHV-6 as the cause of any given clinical
syndrome in older patients.
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Exanthem subitum (also known commonly as roseola
infantum) is a common acute febrile illness of infants
and young children characterized by 3 to 5 days of fever ...