We have been engaged in the molecular and epidemiologic characterization of the Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8), a new human herpesvirus identified in our laboratory. KSHV is strongly associated with Kaposi's sarcoma, the most common AIDS related malignancy. KSHV serologic studies have demonstrated that seroconversion to KSHV antibody positivity occurs prior to KS onset, primarily in adulthood, and that infection rates follow epidemiologic and geographic risk groups for KS. KSHV is also the cause of two lymphoproliferative disorders: a form of non-Hodgkin's B-cell primary effusion (body cavity-based) lymphoma and a subtype of Castleman's disease (MCD).
Sequencing and annotation of the KSHV genome indicates KSHV has a genomic organization similar to two other gammaherpesviruses which cause neoplasms: Epstein-Barr virus and herpesvirus saimiri. The KSHV genome contains a remarkable array of cellular gene homologs, encoding proteins involved in cell cycle regulation or cell signaling. Homologs to human intra- and intercellular regulatory genes include two functional proto-oncogenes (cyclin D and bcl-2), three cyto-/chemokines (IL-6 and MIP-1a), a G-protein coupled receptor, and an interferon regulatory factor. These virus encoded genes directly impact cell cycle, programmed cell death, cell proliferation and immunoregulatory functions in the infected host cell. This extensive array of molecular piracy suggests that the virus may markedly modify the host cell environment contributing to its pathogenesis. Beyond providing pathogenic insights into KS and primary effusion lymphomas, KSHV promises to be an important new model for virus-induced tumorigenesis.