Cellular localization of human herpesvirus-6 in the brains of children with AIDS encephalopathy

Abstract

Human herpesvirus-6, the etiologic agent of exanthem subitum, is a ubiquitous virus that infects almost all children by the age of 2 years and that has previously been shown to be neuroinvasive. These characteristics suggest that human herpesvirus-6 may be important in the neuropathogenesis of acquired immune deficiency syndrome (AIDS) in children. To address this hypothesis, we evaluated postmortem pediatric brain tissues for the presence of human herpesvirus-6 infection. Using in situ hybridization with a digoxigenin-labeled DNA probe for the large tegument protein gene of human herpesvirus-6, we detected nuclear signals in postmortem brain tissue from 4/5 children with human immunodeficiency virus-1 encephalitis. Human herpesvirus-6 DNA was found in numerous oligodendrocytes of the white matter and less frequently in astrocytes, macrophages, microglia and neurons. The human herpesvirus-6 positive cells detected by in situ hybridization were not immunoreactive either for human herpesvirus-6 early nuclear phosphoproteins or for surface glycoproteins associated with productive infection. Only rare human herpesvirus-6 infected cells were found in age-matched control brain tissues. No human herpesvirus-6 infected cells were found in human fetal brain tissue. These data suggest that human herpesvirus-6 is more extensively disseminated in neural cells in the presence of human immunodeficiency infection and immunodeficiency in pediatric AIDS patients, and it may contribute to the pathogenesis of AIDS encephalopathy.