Child and adult forms of human herpesvirus 6 encephalitis: looking back, looking forward

Purpose of reviewThis review evaluates publications on human herpesvirus 6 (HHV-6) encephalitis recognizing firstly that HHV-6A and HHV-6B are separate species with differing properties, and secondly the phenomenon of chromosomal integration; this occurs in a minority of persons and the complete viral genome of either HHV-6A or HHV-6B is present in every nucleated cell in the body. Although chromosomal integration has not been associated with disease, the resulting very high level of viral DNA in human tissues and blood has sometimes been wrongly misinterpreted as active infection.Recent findingsNo disease has been linked to HHV-6A, whereas HHV-6B may cause encephalitis. Encephalitis due to primary HHV-6B infection in young children is commonly reported from Japan, but very rarely elsewhere in the world, suggesting a genetic predisposition. Reports of HHV-6A or HHV-6B encephalitis in immunocompetent older children/adults are most likely due to chromosomal integration and not active infection. HHV-6B reactivation is well established as causing limbic encephalitis after haematopoietic stem cell transplantation, particularly after receipt of cord blood; the outcome is poor and preventive strategies are ineffective.SummaryUnderstanding the pathophysiology of HHV-6B encephalitis remains incomplete, especially regarding young children. Clinical trials of antiviral therapy are warranted for treatment and prevention of HHV-6B encephalitis after transplantation.