Adenovirus-specific translation by displacement of kinase Mnk1 from cap-initiation complex elF4F

Translation of cellular mRNAs involves formation of a cap-binding: translat ion initiation complex known as eIF4F, containing phosphorylated cap-bindin g protein eIF4E, eIF4E kinase Mnk1, eIF4A, poly(A)-binding protein and eIF4 G, Adenovirus is shown to prevent cellular translation by displacing Mnk1 f rom eIF4F, thereby blocking phosphorylation of eIF4E, Overexpression of an eIF4E mutant that cannot be phosphorylated by Mnk1 impairs translation of c ellular but not viral late mRNAs, Adenovirus 100k protein is shown to bind the C-terminus of eIF4G ill vivo and in vitro, the same region bound by Mnk 1, bl vivo, 100k protein displaces Mnk1 from eIF4G during adenovirus infect ion, or in transfected cells. Purified 100k protein also evicts Mnk1 from i solated eIF4F complexes ira vitro. A mutant adenovirus with a temperature-s ensitive 100k protein that cannot inhibit cellular protein synthesis at res trictive temperature no longer blocks Mnk1 binding to eIF4G, or phosphoryla tion of eIF4E, We describe a mechanism whereby adenovirus selectively inhib its the translation of cellular but not viral mRNAs by displacement of Mnk1 from eIF4G and inhibition of eIF4E phosphorylation.