The pathogenic role of HHV-8 in other malignancies, such as multicentric Castleman's disease and primary effusion lymphoma, was again based on molecular, seroepidemiological, and cell biology studies ( 264). This association has been supported both by molecular analysis ( 33, 50, 212, 262) and by seroepidemiological studies ( 11, 51, 134, 258, 263). In situ hybridization techniques have pinpointed the location of HHV-8 in the vascular endothelial cells and perivascular spindle-shaped cells in KS lesions ( 31, 172). Since its initial discovery, HHV-8 has been found in all forms of KS: classical, endemic, and AIDS-associated iatrogenically acquired KS ( 265). ( 56) in Kaposi's sarcoma (KS) tissues from a patient with AIDS by representational difference analysis. In the rest of the world, the seroprevalency is low, 2 to 5% ( 58). Geographic pockets in this area with higher or lower prevalences can be found. From 10 to 25% of people from the Mediterranean area are seropositive for the virus. In sub-Saharan Africa, antibodies to HHV-8 can be found in upwards of 30% of the general population ( 55, 134, 258, 263). Because they are so common, it has been very difficult to prove their role in the pathogenesis of malignant or nonmalignant diseases.Īn important exception to this rule, because of its limited and uneven distribution, is human herpesvirus 8 (HHV-8), also called Kaposi's sarcoma-associated herpesvirus (KSHV). This shedding is responsible for horizontal primary transmission, usually from mother to child, so that initial infection occurs very early in life. They usually persist as long-term latent infections, and asymptomatic shedding of infectious virus is common. Most human herpesviruses are ubiquitous in most populations. In this article, we review the biology, molecular virology, epidemiology, transmission, detection methods, pathogenesis, and antiviral therapy of this newly discovered human herpesvirus. It is not, however, sufficient for transformation, and other cofactors such as immunosuppressive cytokines are involved in the development of HHV-8-associated malignancies. HHV-8 is a transforming virus, as evidenced by its presence in human malignancies, by the in vitro transforming properties of several of its viral genes, and by its ability to transform some primary cells in culture.
This virus can be transmitted both sexually and through body fluids (e.g., saliva and blood). The seroprevalence of HHV-8, based on detection of latent and lytic proteins, is 2 to 5% in healthy donors except in certain geographic areas where the virus is endemic, 80 to 95% in classic KS patients, and 40 to 50% in HIV-1 patients without KS. In addition, HHV-8 DNA sequences have been found in association with other diseases, but the role of the virus in these diseases is largely unconfirmed and remains controversial.
HHV-8 is strongly associated with all subtypes of Kaposi's sarcoma (KS), multicentric Castleman's disease, and a rare form of B-cell lymphoma, primary effusion lymphoma.
Unlike other human herpesviruses (herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, cytomegalovirus, HHV-6, and HHV-7), it is not widespread in the general population and has many unique proteins. Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), discovered in 1994, is a human rhadinovirus (gamma-2 herpesvirus).