Translation of Viral mRNA without Active eIF2: The Case of Picornaviruses

Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain.
PLoS ONE (Impact Factor: 3.53). 07/2011; 6(7):e22230. DOI: 10.1371/journal.pone.0022230
Source: PubMed

ABSTRACT Previous work by several laboratories has established that translation of picornavirus RNA requires active eIF2α for translation in cell free systems or after transfection in culture cells. Strikingly, we have found that encephalomyocarditis virus protein synthesis at late infection times is resistant to inhibitors that induce the phosphorylation of eIF2α whereas translation of encephalomyocarditis virus early during infection is blocked upon inactivation of eIF2α by phosphorylation induced by arsenite. The presence of this compound during the first hour of infection leads to a delay in the appearance of late protein synthesis in encephalomyocarditis virus-infected cells. Depletion of eIF2α also provokes a delay in the kinetics of encephalomyocarditis virus protein synthesis, whereas at late times the levels of viral translation are similar in control or eIF2α-depleted HeLa cells. Immunofluorescence analysis reveals that eIF2α, contrary to eIF4GI, does not colocalize with ribosomes or with encephalomyocarditis virus 3D polymerase. Taken together, these findings support the novel idea that eIF2 is not involved in the translation of encephalomyocarditis virus RNA during late infection. Moreover, other picornaviruses such as foot-and-mouth disease virus, mengovirus and poliovirus do not require active eIF2α when maximal viral translation is taking place. Therefore, translation of picornavirus RNA may exhibit a dual mechanism as regards the participation of eIF2. This factor would be necessary to translate the input genomic RNA, but after viral RNA replication, the mechanism of viral RNA translation switches to one independent of eIF2.

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Available from: Miguel Angel Sanz, Aug 15, 2015
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    • "Another translation initiation factor eIF4GII as well as the Poly-(A) binding protein (PABP), a protein facilitating the formation of a closed translation initiation loop by interaction of the 5 and 3 ends of the mRNA, has been reported to be cleaved by picornaviral 2A (Gradi et al., 1998; Joachims et al., 1999). All these cleavages often correspond with a translational shift to IRES-dependent translation (Redondo et al., 2011; Welnowska et al., 2011). Another group also showed that the shift in translation seen during the later phase of poliovirus infection is not entirely due to phosphorylation (inactivation) of eIF2α (see Discussion in later session), but may also depend upon protease 3C activation and cleavage of another translation initiation factor, eIF5B, to a C-terminal truncated version thought to replace eIF2 during translation (White et al., 2011). "
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