RAPAMYCIN STIMULATES VIRAL PROTEIN-SYNTHESIS AND AUGMENTS THE SHUTOFFOF HOST PROTEIN-SYNTHESIS UPON PICORNAVIRUS INFECTION

The immunosuppressant drug rapamycin blocks progression of the cell cy cle at G(1) in mammalian cells and yeast, We recently showed that rapa mycin inhibits both in vitro and in vivo cap-dependent, but not cap-in dependent, translation, This inhibition is causally related to reduced phosphorylation and consequent activation of 4E-BP1, a repressor of t he function of the cap-binding protein, eIF4E. Two members of the pico rnavirus family, encephalomyocarditis virus and poliovirus, inhibit ph osphorylation of 4E-BP1, Since translation of picornavirus mRNAs is ca p independent, inhibition of phosphorylation of 4E-BP1 could contribut e to the shutoff of host protein synthesis, Here, we show that rapamyc in augments both the shutoff of host protein synthesis and the initial rate of synthesis of viral proteins in cells infected with encephalom yocarditis virus and poliovirus.