Roseolovirus-associated Encephalitis in Immunocompetent and Immunocompromised Individuals

The roseoloviruses, human herpesvirus (HHV)-6A, HHV-6B, and HHV-7, can cause severe encephalitis or encephalopathy. In immunocompetent children, primary HHV-6B infection is occasionally accompanied by diverse clinical forms of encephalitis. Roseolovirus coinfections with heterologous viruses and delayed primary HHV-7 infection in immunocompetent adults result in very severe neurological and generalized symptoms. Recovery from neurological sequelae is slow and sometimes incomplete. In immunocompromised patients with underlying hematological malignancies and transplantation, frequent single or simultaneous reactivation of roseoloviruses elicit severe, lethal organ dysfunctions, including damages in the limbic system, brain stem, and hippocampus. Most cases have been due to HHV-6B with HHV-6A accounting for 2-3%. The most severe manifestation of HHV-6B reactivation is post-transplantation limbic encephalitis. Seizures, cognitive problems, and abnormal EEG are common. Major risk factors for HHV-6B-associated encephalitis include unrelated cord blood cell transplantation and repeated hematopoietic stem cell transplantation. Rare genetic disorders, male gender, certain HLA constellation, and immune tolerance to replicating HHV-6 in persons carrying chromosomally integrated HHV-6 might also predispose an individual to roseolovirus-associated brain damage. At this time, little is known about the risk factors for HHV-7-associated encephalitis. Intrathecal glial cell destruction due to virus replication, overexpression of proinflammatory cytokines, and viral mimicry of chemokines all contribute to brain dysfunction. High virus load in the cerebrospinal fluid, hippocampal astrogliosis, and viral protein expression in HHV-6B-associated cases and multiple microscopic neuronal degeneration in HHV-7-associated cases are typical laboratory findings. Early empirical therapy with ganciclovir or foscarnet might save the life of a patient with roseolovirus-associated encephalitis.