Figure 1

Mechanisms used by different classes of human herpesviruses to modulate the Rb-E2F pathway. See text for details. α. HSV-1 prevents Rb phosphorylation and keeps cellular Cdks inactive, likely through the downregulation of cyclin proteins and the mislocalization of Cdks. VZV infected cells display Cdk activity even though p21 and p27 are induced. However, Rb remains unphosphorylated through an uncharacterized mechanism.β. HMCV infected cells show a lack of hypophosphorylated Rb and high levels of hyperphosphorylated Rb, due to both pp71-mediated degradation and UL97-mediated phosphorylation. IE2 can also directly activate E2F-responsive genes.γ. EBV has multiple proteins (Z, R, LMP-1, EBNA-2,-3C,-5) that could lead to the phosphorylation of Rb by cellular Cdks, and/or may directly phosphorylate Rb thropugh the function of the viral kinase, BGLF-4. KSHV can activate the Rb pathway by LANA-mediated disruption of Rb-E2F complexes, or by direct phosphorylation of Rb through the action of the v-cyclin and/or the ORF36 proteins.