Endothelial progenitors from the peripheral blood of patients with classic Kaposi’s sarcoma are persistently infected by KSHV

Accumulating evidence indicates that tumor angiogenesis is supported by the mobilization and incorporation of endothelial progenitor cells (EPCs), highly proliferative precursors of bone marrow origin. Our recent demonstration that EPCs are increased in the peripheral blood of patients with Kaposi’s sarcoma (KS), together with the intrinsic biologic properties of these cells, strongly suggests that EPCs could be involved in the pathogenesis of KS. The fact that the characteristic spindle cells share many markers with vascular endothelial cells and are thought to be of endothelial origin further supports this hypothesis. A possible scenario may be that EPCs may act as preferential KSHV reservoirs and, whether infected, may home to permissive sites and propagate to produce KS lesions. Novel insights into the state of KSHV infection of EPCs could greatly improve the comprehension of KS pathogenesis. Therefore, we investigated KSHV infection of ex-vivo cultured late-EPCs that, among other cell populations with endothelial features, contribute more directly to neovascularization and might represent a major source of endothelial progenitors in vivo. We found that late-EPCs from KS patients harbor KSHV DNA and retain the virus after multiple passages. Lytic phase induction or hypoxia could amplify the virus in cells and supernatants, indicating that late-EPCs support KSHV productive replication. EPCs appear therefore to represent potential virus reservoirs and putative precursors of KS spindle cells. The biological mechanisms that govern the infection of EPC by KSHV are currently under investigation.