A subunit of
eukaryotic initiation factor-4F (eIF-4F) which is a component of the
protein complex which binds to the methylated cap structure at the 5' end of most cellular mRNAs, is proteolytically cleaved in poliovirus-infected cells resulting in the shutoff of cellular
protein synthesis. Poliovirus
mRNA is selectively translated in infected cells, in part, because translation of the uncapped viral
mRNA does not require an intact
cap binding protein complex. Wild-type poliovirus also inhibits the translation of
vesicular stomatitis virus (VSV) mRNAs in coinfected cells, however, it has been unclear whether similar mechanisms are employed by poliovirus to interfere with cellular and VSV
protein synthesis. Degradation of
eIF-4F appears to be an indirect function of the poliovirus-encoded
protease 2A. A poliovirus mutant in 2A failed to mediate
eIF-4F cleavage and selectively terminate translation of capped cellular mRNAs. Unlike wild-type poliovirus, 2A-1 does not interfere with VSV-specified
protein synthesis. These results indicate that the same
viral protein, 2A
protease, is required not only to effectively terminate host
protein synthesis, but also to interfere with expression of a heterologous virus, VSV. In addition, 2A-1 specifies a function, heretofore undescribed for poliovirus, which interferes with VSV-induced shutoff of
protein synthesis.