Inflammatory reactivation and angiogenicity of KSHV/HHV8. A hypothesis for KS pathogenesis emerging from the observations by Aoki et al9 and Monini et al.10 When circulating KS-progenitors and cells latently infected with KSHV home to inflammatory sites, the exposure to ICs such as γIFN causes their differentiation into KS-like spindle cells and induces KSHV reactivation. Reactivation of KSHV could lead to the expression of potentially pathogenic early genes such as vIL-6 that can activate VEGF and induce angiogenesis. Viral lytic replication in the same cells can activate inflammation, which may also play a proangiogenic role. The creation of this inflammatory-angiogenic environment increases the availability of infectable cells such as endothelial cells and KS-spindle cells that will end up in the development of the KS lesion.