Human herpesvirus 8-encoded proteins with potential roles in virus-associated neoplasia

Human herpesvirus 8 ( HHV- 8) is a gamma- 2 herpsvirus, related genetically to simian herpesvirus saimiri ( HVS), the prototype virus of this subgroup of the gammaherpesvirus subfamily. HHV- 8 DNA is present in all forms of Kaposis's sarcoma ( KS) and primary effusion lymphoma ( PEL), and in most forms of multicentric Castleman's disease ( MCD), especially in HIV infected individuals. Of relevance to attempts to explain the molecular basis of HHV- 8 associated neoplasia, are the unique genes specified by this virus, in particular angiogenic cytokines viral interleukin- 6 ( vIL- 6) and viral CC- class chemokines ( vCCL- 1, vCCL- 2, vCCL- 3), mitogenic signaling membrane proteins variable ITAMcontaining protein ( VIP) and latency associated membrane protein ( LAMP), pro- survival latently- expressed viral interferon regulatory factor ( vIRF3), and the kaposin family of proteins that promote cell growth and cytokine production. Also of relevance are the angiogenic and cytokine-inducing viral G protein- coupled receptor ( vGPCR), pro- proliferative and pro- survival latency proteins viral FLICE inhibitory protein ( vFLIP) and latency- associated nuclear antigen ( LANA), and G1- S phase cell- cycle promoter viral cyclin ( v- cyclin), proteins specified also by other gamma- 2 herpesviruses. The enormous progress on the characterization of the properties and biological activities of these proteins over the last ten years has provided insight into the potential mechanisms of HHV- 8- induced neoplasia. Present data suggest that there operates a combination of cell transformation mediated by latently expressed proteins that promote cell proliferation and survival coupled with paracrine signaling functions mediated by either the viral cytokines or viral receptor- induced secreted cellular proteins. This review discusses the properties of the viral proteins believed to contribute to viral neoplasia via these mechanisms.