The role of human herpesvirus 8 in the pathogenesis of Kaposi's sarcoma.

Human herpesvirus 8 is a novel gamma-herpesvirus that has been linked with all clinical types of KS through both DNA and serologic studies. By electron microscopic, in situ hybridization, and in situ PCR studies, virus is found in tumor spindle cells, in normal-appearing endothelial cells within lesions, and in tumor-infiltrating leukocytes. The fact that most tumor cells are latently, as opposed to lytically, infected with HHV8 makes the possibility of treating KS patients with antiherpesviral medications unlikely. Human herpesvirus 8 infection is also associated with BCBL and CD and has recently been reported in patients with multiple myeloma and sarcoidosis (although these latter associations have not been substantiated). Interestingly, the HHV8 genome contains many genes that could be involved in evading normal immune surveillance. Importantly, B-cell lines derived from patients with BCBL have been extremely useful in elucidating the virologic and biological properties of HHV8. In summary, both HHV8 gene analyses and clinico-epidemiologic studies generated by many research teams throughout the world support the concept that HHV8 is the etiologic agent of KS. Future research will focus on developing in vitro model systems to study KS, delineating the expression pattern and function of HHV8-encoded proteins in vivo, determining factors that lead to the development of KS in HHV8-infected individuals, and devising novel therapeutic strategies for KS based on these advances in basic science.