FIG. 10.

Schematic representation depicting the mode of action of angiogenin in maintaining latency. The results presented in the present studies demonstrate the following: KSHV-upregulated angiogenin is expressed both during de novo KSHV infection and in latently infected cells. Angiogenin induces PLC-γ phosphorylation, which in turn is required for nuclear translocation of angiogenin. PLC-γ phosphorylation also results in AKT phosphorylation, which is required for cell survival, and ERK phosphorylation, which is necessary for latent gene expression and for the establishment of latency. Neomycin treatment blocked nuclear translocation of angiogenin and inhibited PLC-γ and AKT phosphorylation, leading to cell death, reduction in latent gene expression, and an increase in lytic gene expression. U73122, a conventional PLC-γ inhibitor, reduced cell survival, blocked latent gene expression, and induced lytic gene expression. Angiogenin silencing also reduced cell survival, blocked latent gene expression, and increased lytic gene expression. Collectively, these studies show that KSHV-induced angiogenin plays roles in the maintenance of latency via the PLC-γ pathway.