Poliovirus protease 2A is required for interference with vesicular stomatitis virus-specified protein synthesis.

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.