Document Detail

Promotion of viral IRES-mediated translation under amino acid starvation.
MedLine Citation:
PMID:  22302880     Owner:  NLM     Status:  Publisher    
Cap-dependent and internal ribosomal entry site (IRES)-mediated translation are regulated differently within cells. Viral IRES-mediated translation often remains active when cellular cap-dependent translation is severely impaired under cellular stresses induced by virus infection. To investigate how cellular stresses influence efficiency of viral IRES-mediated translation, we used bicistronic luciferase reporter construct harboring IRES elements from the following viruses: encephalomyocarditis virus (EMCV), foot and mouth disease virus (FMDV), hepatitis C virus (HCV) or human rhinovirus (HRV). NIH3T3 cells transfected with these bicistronic reporter constructs were subjected to different cellular stresses. Increased translation initiation was only observed under amino acid starvation when EMCV or FMDV IRES elements were present. To identify cellular mechanisms that promoted viral IRES-mediated translation, we tested the involvement of eukaryotic initiation factor 4E binding protein (4E-BP), general control nondepressed 2 (GCN2) and eukaryotic initiation factor 2B (eIF2B), since these are known to be modulated under amino acid starvation. Knockdown of 4E-BP1 impaired the promotion of EMCV and FMDV IRES-mediated translation under amino acid starvation while GCN2 and eIF2B were not involved. To further investigate how 4E-BP1 regulate translation initiated by EMCV and FMDV IRES elements, we used a phosphoinositide kinase-3 inhibitor (LY294002), an mTOR inhibitor (Torin1) or leucine starvation to mimic 4E-BP1 dephosphorylation induced by amino acid starvation. 4E-BP1 dephosphorylation induced by the treatments was not sufficient to promote the viral IRES-mediated translation. These results suggest that 4E-BP1 regulates EMCV and FMDV IRES-mediated translation under amino acid starvation, but not via its dephosphorylation.
Maria Licursi; Yumiko Komatsu; Theerawat Pongnopparat; Kensuke Ken Hirasawa
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-1
Journal Detail:
Title:  The Journal of general virology     Volume:  -     ISSN:  1465-2099     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077340     Medline TA:  J Gen Virol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Memorial University of Newfoundland, St. John's, NL, Canada.
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