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.