HHV6, first isolated in 1986 from lymphocytes, is a widespread betaherpesvirus genetically related to human cytomegalovirus (HCMV).
Two major species HHV-6A and HHV-6B are recognised. They differ at biological, immunological and molecular levels as well as prevalence and disease association. Most viral isolates responsible for symptomatic primary infection belong to the B sub-group. A sub-group isolates have been less commonly detected in immunosuppressed adults.
HHV6 induces a lifelong latent infection in humans. Unlike other human herpesviruses, genomic HHV-6 is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the population. Although infrequent, this may be a confounding factor for the diagnosis of active viral infection.
The
primary clinical manifestations
in early childhood include
exanthem subitum
(
Roseola
/rash) characterised by high fever, sometimes with seizures, generalised rash and granulocytopenia.
Meningoencephalitis, fulminant hepatitis and other organ involvement are rarer complications of primary infection.
Approximately 75% of people are infected by one year of age with HHV6 which thereafter persists for life.
Infection or reinfection
is generally associated with some immunological abnormality and in immunosuppressed hosts fever, rash, encephalitis, pneumonitis, transplant rejection-especially renal and bone marrow- are associated with HHV6 infection.
Laboratory diagnosis in immunosuppressed patients by seroconversion or qualitative PCR are not ideal clinically due to high rate of seropositivity (approaching 100% at age 2 years) and frequency of positive PCR in sites such as blood, saliva and brain.
Quantitative and real-time PCR may be more useful for
delineating
disease associations by following viral load in blood. Note that in chromosomally integrated HHV-6, each cell contains a copy of HHV-6. High levels of HHV-6 (>million copies per ml whole blood) therefore pose a diagnostic problem and are highly suggestive of ciHHV-6.
The antiviral compounds ganciclovir, foscarnet and cidofovir are effective against active HHV-6 infections but indications tor treatment are not formally approved to date.
