Human herpesviruses: Human herpesvirus 6

Abstract

A snapshot of human herpesvirus 6 (HHV-6) reveals several key features of this virus that are clearly established. HHV-6 causes ubiquitous infection in infancy or early childhood that is typically a self-limited illness and generally associated with complete recovery. Following primary infection HHV-6 remains latent or persistent at several different sites including the peripheral blood mononuclear cells, the salivary glands, the female genital tract, and the central nervous system. Reactivation of HHV-6 occurs during periods of immune compromise and is associated with disease. However, the biography of HHV-6 is rapidly evolving. Increasing interest and research recently have allowed a better understanding of HHV-6's import and pathogenesis. New molecular techniques for detection and determining viral state have further defined the epidemiologic and clinical patterns of HHV-6 according to age, presence, and replicative state in different body sites and whether infection is new or reactivated. Taken together, these new findings have led to the classification of the two variants, HHV-6 A and HHV-6 B, into distinct species. Also of particular note are new data concerning HHV-6's unique ability to integrate into human chromosomes. Human telomeres appear to be the consistent site of integration of the complete viral genome, which raises the possibility of disruption of the vital functions of the telomeres. In addition, new evidence indicates that the chromosomal integration of HHV-6 passed through the germline causes the great majority of congenital HHV-6 infections and that even transplacentally acquired congenital HHV-6 infections may occur from chromosomally integrated virus. Unknown, however, is the outcome of infants with congenital infection from chromosomally integrated HHV-6 and the pathogenic ramifications of the lifelong presence of virus which is integrated in an individual's chromosomes. Other important areas that remain unresolved despite recent research include the definitive distinction between disease which is due to the direct or indirect effects of HHV-6 infection versus when HHV-6 DNA is detected, but unrelated to disease. The ubiquity of HHV-6 infections, its wide tropism, and its subsequent latency confound this distinction and indicate that currently the diagnosis of HHV-6 disease cannot be made on the basis of HHV-6 DNA detection alone. Yet needed are not only clinically relevant diagnostic assays that are feasible and rapidly available but also effective prophylactic and therapeutic approaches for HHV-6, especially among high-risk immunocompromised individuals. Although ganciclovir, foscarnet, and cidofovir have been shown in vitro to be active against HHV-6 infection, large controlled clinical trials have not been done. Most critical are efforts to increase recognition that understanding the immunopathogenesis of HHV-6 is important and that sufficient economic support is integral to this goal.