KSHV is of the and is a lymphotropic herpesvirus. KSHV (also known as human herpesvirus 8 or HHV-8) is associated with the malignancies Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL) and plasmablastic variant multicentric Castleman’s disease. Viral spead is believed to occur predominantly through saliva. Seropositivity in homosexual AIDS patients is as high as 85%. KSHV has several genes which are molecular mimicks of the host including vIL-6, vIL-8R, v-cyclin, vIRFs.
Latency is in B cells and is associated with LANA (latency-associated nuclear antigen) which maintains the viral episome, binds and inactivates and the . The first functional role demonstrated for LANA was tethering of KSHV episomal genomes to host chromosomes to facilitate viral DNA replication and effective segregation of genomes to daughter cells and hence ensure viral persistence in latently infected cells. Subsequently, LANA was shown to bind to p53 and to the phophosphorylated form of pRb, properties that are consistent with a role in promoting cell cycle progression. More recently, LANA was found to mediate stabilization of ?-catenin, the nuclear effector of the canonical Wnt signaling pathway. Accumulation of cytosolic ?-catenin allows entry into the nuclear, where B-catenin interacts with Tcf/Lef family transcription factors to stimulate expression of cellular genes whose promoters contain Tcf/Lef binding sites.
KS is frequent in AIDS and transplant patients. It is a relatively benign tumor in age 65 and older males. KS is a highly vascularized lesion characterized by the presence of spindle cells.
Anti-retrovirus therapy in AIDS patients leads to tumor regression. GCV prevents tumor development but has no effect on existing tumors.