Phosphorylation state of the cap-binding protein eIF4E during viral infection.
The eukaryotic translation initiation factor eIF4E, the cap-binding protein, seems to play an essential role in the establishment of the host shut-off after viral infection. Infection with adenovirus and influenza virus caused dephosphorylation of eIF4E and an involvement of a viral protein was suggested. In this report, we studied several other viruses for their ability to change the phosphorylation state of eIF4E, and we looked for the mechanism of eIF4E dephosphorylation. First, it was shown that after encephalomyocarditis virus (EMCV) and poliovirus infection, dephosphorylation of eIF4E occurred. Dephosphorylation of eIF4E was not observed after Semliki Forest virus and reovirus infection. An artificial increase of the level of phosphorylated eIF4E by treating the cells with the phosphatase inhibitor okadaic acid changed neither the kinetics of EMCV and poliovirus infection, nor that of host shut-off. Infections with the uv-treated EMCV showed that the virus binding or entry into the cell initiates eIF4E dephosphorylation. Besides this entry-induced eIF4E dephosphorylation, dephosphorylation was also induced by blocking protein synthesis with the initiation inhibitor pactamycin, or with the elongation inhibitor cycloheximide. We conclude that eIF4E is dephosphorylated by entry of EMCV, and the effect is strengthened by the decrease in cap-dependent translation.
Kleijn
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Department of Molecular Cell Biology, University of Utrecht, The Netherlands.
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D018354:Alphavirus Infections / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D018188:Cardiovirus Infections / Q000378:metabolism; D006224:Cricetinae; D004686:Encephalomyocarditis virus; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D039561:Eukaryotic Initiation Factor-4E; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D019319:Okadaic Acid; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D011051:Poliomyelitis / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D012088:Reoviridae Infections / Q000378:metabolism; D012672:Semliki forest virus; D014407:Tumor Cells, Cultured; D014777:Virus Diseases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D010455:Peptides; D047428:Protein Kinase Inhibitors; D019319:Okadaic Acid