Human Herpesvirus-8

HUMAN HERPESVIRUS-8

Human herpesvirus-8 (Kaposi’s sarcoma–associated herpesvirus, or KSHV; HHV-8) was discovered in 1994 by identification of unique viral DNA sequences in Kaposi’s sarcoma tissue obtained from an AIDS patient, using subtractive hybridization analysis. These spe-cific DNA sequences are found in 95% or more of Kaposi’s sarcoma tissues, both AIDS related and non-AIDS in African cases. KSHV DNA has also been detected in cells from lymphoproliferative diseases (eg, primary effusion lymphomas, associated with AIDS and multicentric Castleman’s disease).

Recently, HHV-8 was isolated in culture, and when characterized, it seems most closely related to EBV. Like EBV, the virus preferentially infects B lymphocytes and it is also considered to be a gamma herpes virus. Epidemiologic and virologic studies suggest that it is a necessary but perhaps not sufficient cause of Kaposi’s sarcoma and that other factors (eg, immunosuppression, genetic predisposition) are cofactors in the development of this malignancy. On average, seropositivity to HHV-8 precedes the development of Kaposi’s sarcoma by 3 years. The virus appears to be sexually transmitted, as suggested by a higher prevalence of antibody in promiscuous gay men than those who are not promiscuous, and by higher prevalence in gay men with HIV versus other HIV-positive risk groups, such as transfusion recipients and hemophiliacs. Specific and sensitive anti-body assays are being developed, and antibody to HHV-8 appears to be relatively rare in the general population. It is difficult to assess the impact of antivirals, because Kaposi’s sarcoma may improve with immune reconstitution. Interferon- γcan be effective against

Kaposi’s sarcoma, but this may result from immune enhancement rather than any specific antiviral activity. Evidence of active viral replication in Kaposi’s sarcoma is minimal, so there may not be an appropriate target for antivirals at the time that Kaposi’s sarcoma be-comes manifest.