title: Semliki Forest virus capsid protein inhibits the initiation of translation by upregulating the double-stranded RNA-activated protein kinase (PKR).
abstract: We investigated the possible translational role which elevated concentrations of highly purified Semliki Forest virus (SFV) capsid (C)-protein molecules may play in a cell-free translation system. Here we demonstrate that in the absence of double-stranded RNA high concentrations of C protein triggered the phosphorylation of the interferon-induced, double-stranded RNA-activated protein kinase, PKR. Activated PKR in turn phosphorylated its natural substrate, the alpha subunit of eukaryotic initiation factor 2 (eIF-2), thereby inhibiting initiation of host cell translation. These findings were further strengthened by experiments showing that during natural infection with SFV the maximum phosphorylation of PKR coincided with the maximum synthesis of C protein 4-9 hours post infection. Thus, our results demonstrate that high concentrations of C-protein molecules may act in a hitherto novel mechanism on PKR to inhibit host cell protein synthesis during viral infection.
authors.affiliation: Institute of Medical Microbiology, University of Berne, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Favre
authors.forename: E
authors.initials: E
authors.lastname: Studer
authors.forename: M R
authors.initials: MR
authors.lastname: Michel
mesh_terms: D002213:Capsid / Q000502:physiology*; D002352:Carrier Proteins; D002474:Cell-Free System; D004789:Enzyme Activation; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases; D010766:Phosphorylation; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D012330:RNA, Double-Stranded; D012672:Semliki forest virus / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D014759:Viral Envelope Proteins / Q000502:physiology*; D019892:eIF-2 Kinase
chemical_list: D002352:Carrier Proteins; D012330:RNA, Double-Stranded; D014759:Viral Envelope Proteins; C020723:citrate-binding transport protein; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D005090:Exodeoxyribonucleases; D043211:Exodeoxyribonuclease V