Arginine methylation of the ICP27 RGG box regulates the functional interactions of ICP27 with SRPK1 and Aly/REF during herpes simplex virus 1 infection.

The herpes simplex virus 1 protein ICP27 is methylated on arginine residues within an RGG box, and arginine methylation regulates ICP27 export to the cytoplasm. Arginine methylation can regulate protein-protein interactions; therefore, we examined the effect of hypomethylation on ICP27's interactions with cellular proteins SRPK1 and Aly/REF, which bind to ICP27 through the RGG box region. During infections with viral mutants containing lysine substitutions or the methylation inhibitor adenosine dialdehyde, the interaction of ICP27 with SRPK1 and Aly/REF was decreased, as determined by coimmunoprecipitation and colocalization studies, indicating that ICP27 RGG box methylation regulates interaction with these proteins.