title: Rapamycin stimulates viral protein synthesis and augments the shutoff of host protein synthesis upon picornavirus infection.
abstract: The immunosuppressant drug rapamycin blocks progression of the cell cycle at G1 in mammalian cells and yeast. We recently showed that rapamycin inhibits both in vitro and in vivo cap-dependent, but not cap-independent, translation. This inhibition is causally related to reduced phosphorylation and consequent activation of 4E-BP1, a repressor of the function of the cap-binding protein, eIF4E. Two members of the picornavirus family, encephalomyocarditis virus and poliovirus, inhibit phosphorylation of 4E-BP1. Since translation of picornavirus mRNAs is cap independent, inhibition of phosphorylation of 4E-BP1 could contribute to the shutoff of host protein synthesis. Here, we show that rapamycin augments both the shutoff of host protein synthesis and the initial rate of synthesis of viral proteins in cells infected with encephalomyocarditis virus and poliovirus.
authors.affiliation: Department of Biochemistry, McGill University, Montréal, Québec, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Beretta
authors.forename: Y V
authors.initials: YV
authors.lastname: Svitkin
authors.forename: N
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004686:Encephalomyocarditis virus / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors; D006367:HeLa Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017955:Poliovirus / Q000378:metabolism*; D011090:Polyenes / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D012367:RNA, Viral / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D020123:Sirolimus; D014721:Vesicular stomatitis Indiana virus / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis* / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; D007166:Immunosuppressive Agents; D010750:Phosphoproteins; D011090:Polyenes; D011506:Proteins; D012367:RNA, Viral; D012097:Repressor Proteins; D014764:Viral Proteins; D020123:Sirolimus