Human herpesvirus (HHV)-6 is a β-herpesvirus that infects most infants by 2 years of age and persists in a variety of host cells after primary infection, with intermittent reactivation typically during periods of immunosuppression.
HHV-6 has two closely related species, HHV-6A and B, which are both neurotropic and can be detected in up to 85% of brain samples at autopsy. This pleiotropic virus has been implicated in many central nervous system (CNS) diseases, including febrile seizures (FS), epilepsy due to medial temporal lobe sclerosis, multiple sclerosis, encephalomyelitis, progressive multifocal leukoencephalopathy, chronic fatigue syndrome, and cognitive dysfunction.
The significance of HHV-6 infection is often controversial due to the challenge implicit in attributing disease to a commensal virus of the brain. Studies have used a variety of unstandardized techniques on an array of sample sources to detect HHV-6, making direct comparisons problematic. In addition, many detection methods do not distinguish between latent and active infection. However, there is accumulating evidence implicating HHV-6 as a cause of CNS pathology, especially in FS and encephalitis.
Treatment options are limited, fraught with side-effects, and poorly studied. Whether HHV-6 is a commensal pathogen of the brain, marker of immune dysregulation, trigger of autoimmunity, or directly neurotoxic mediator of CNS disease will remain uncertain for many CNS diseases until more refined studies are performed.
Human herpesvirus 6 and the nervous system, by JA Hill and N Venna in Handb Clin Neurol. 2014; 123: 327-55