Pseudorabies virus glycoprotein gE triggers ERK1/2 phosphorylation and degradation of the pro-apoptotic protein Bim in epithelial cells

• PRV triggers gE-mediated ERK1/2 phosphorylation in PK-15 cells.
• This ERK1/2 phosphorylation is associated with degradation of pro-apoptotic Bim.
• Removal of the cytoplasmic domain of gE is associated with more pronounced cell surface expression of gE, ERK1/2 phosphorylation and Bim degradation.

ERK1/2 (Extracellular signal Regulated Kinase 1/2) signaling is a key cellular signaling axis controlling many cellular events, including cell survival. Activation of ERK 1/2 may trigger an anti-apoptotic response, and different viruses have been shown to benefit from this process. We have described recently that the viral glycoprotein gE mediates pseudorabies virus (PRV)-induced activation of ERK 1/2 in T lymphocytes. In the present study, we report that PRV gE-mediated ERK 1/2 phosphorylation also occurs in epithelial cells and that in these cells, gE-mediated ERK 1/2 signaling is associated with degradation of the pro-apoptotic protein Bim. Our results for the first time link the viral glycoprotein gE, an important alphaherpesvirus virulence factor, with the apoptotic signaling pathway.