Promotion of viral internal ribosomal entry site-mediated translation under amino acid starvation

• DOI: 10.1099/vir.0.040386-0
• Publication Date: 2012-02-02T19:54:56Z
• Authors: Maria Licursi; Yumiko Komatsu; Theerawat Pongnop...; Kensuke Hirasawa
• Keywords: Picornavirus; Initiation factor; Eukaryotic initiation factor; Eukaryotic translation

Cap-dependent and internal ribosomal entry site (IRES)-mediated translation are regulated differently within cells. Viral IRES-mediated often remains active when cellular cap-dependent is severely impaired under stresses induced by virus infection. To investigate how influence the efficiency of viral translation, we used a bicistronic luciferase reporter construct harbouring IRES elements from following viruses: encephalomyocarditis (EMCV), foot-and-mouth disease (FMDV), hepatitis C (HCV) or human rhinovirus (HRV). NIH3T3 cells transfected with these constructs were subjected to different stresses. Increased initiation was only observed amino acid starvation EMCV FMDV present. identify mechanisms that promoted tested involvement eukaryotic factor 4E-binding protein (4E-BP), general control non-depressed 2 (GCN2) 2B (eIF2B), as known be modulated starvation. Knockdown 4E-BP1 promotion starvation, whereas GCN2 eIF2B not involved. further regulates initiated elements, phosphoinositide kinase-3 inhibitor (LY294002), an mTOR (Torin1) leucine mimic dephosphorylation treatments sufficient promote translation. These results suggest but via its dephosphorylation.