PHOSPHORYLATION STATE OF THE CAP-BINDING PROTEIN EIF4E DURING VIRAL-INFECTION

The eukaryotic translation initiation factor elF-4E, the cap-binding p rotein, seems to play an essential role in the establishment of the ho st shut-off after viral infection. Infection with adenovirus and influ enza virus caused dephosphorylation of elF4E and an involvement of a v iral protein was suggested. In this report, we studied several other v iruses for their ability to change the phosphorylation state of elF4E, and we looked for the mechanism of elF4E dephosphorylation. First, it was shown that after encephalomyocarditis virus (EMCV) and poliovirus infection, dephosphorylation of elF4E occurred. Dephosphorylation of elF4E was not observed after Semliki Forest virus and reovirus infecti on. An artificial increase of the level of phosphorylated elF4E by tre ating the cells with the phosphatase inhibitor okadaic acid changed ne ither the kinetics of EMCV and poliovirus infection, nor that of host shut-off. infections with uv-treated EMCV showed that virus binding or entry into the cell initiates elF4E dephosphorylation. Besides this e ntry-induced elF4E dephosphorylation, dephosphorylation was also induc ed by blocking protein synthesis with the initiation inhibitor pactamy cin, or with the elongation inhibitor cycloheximide. We conclude that elF4E is dephosphorylated by entry of EMCV, and the effect is strength ened by the decrease in cap-dependent translation. (C) 1996 Academic P ress, Inc