Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8): epidemiology and pathogenesis

Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus type 8 (HHV-8), is a gamma(2) herpesvirus (rhadinovirus) and the most recently di scovered human tumour virus. It is involved in the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma and the plasma cell variant of mul ticentric Castleman's disease. KSHV is not pathogenic in most otherwise hea lthy individuals but is highly oncogenic in HIV-1-infected and iatrogenical ly immunosuppressed individuals. It establishes a latent Infection in most KS spindle (endothelial tumour) cells and in the neoplastic B cells of prim ary effusion lymphomas. The KSHV genome contains several homologues of cell ular genes known to regulate cell growth and differentiation. Although some of these have transforming properties in vitro, their precise role in onco genesis is still under Investigation. Other co-factors may be involved in t he pathogenesis of KS ire HIV-uninfected, Immunocompetent individuals, e.g. in African endemic KS, but none have been identified yet. Transmission of KSHV among homosexual men appears to occur through sexual contact, but in e ndemic countries transmission is frequent in childhood and may occur throug h close contact within families. Four major variants of KSHV have been defi ned, on the basis of variability In the K1 gene; they may have co-evolved w ith certain human populations. In addition, some KSHV strains may have resu lted from a recombination event with a related, but not yet identified, gam ma(2) herpesvirus.