THE EIF4G-EIF4E COMPLEX IS THE TARGET FOR DIRECT CLEAVAGE BY THE RHINOVIRUS 2A PROTEINASE

The 2A proteinases (2A(pro)) of certain picornaviruses induce the clea vage of the eIF4G subunit of the cap-binding protein complex, eIF4F. S everal reports have demonstrated that 2A(pro) of rhinovirus and coxsac kievirus B4 cleave eIF4G directly. However, it was suggested that in p oliovirus infection, the 2A(pro) induces the activation of a cellular proteinase which in turn cleaves eIF4G. Furthermore, it is not clear w hether eIF4G is cleaved as part of the eIF4F complex or as an individu al polypeptide. To address these issues, recombinant eIF4G was purifie d from Sf9 insect cells and tested for cleavage by purified rhinovirus 2A(pro). Here we report that eIF4G alone is a relatively poor substra te for cleavage by the rhinovirus 2A(pro). However, an eIF4G-eIF4E com plex is cleaved efficiently by the 2A(pro), suggesting that eIF4F is a preferred substrate for cleavage by rhinovirus 2A(pro), Furthermore, 2A(pro) drastically reduced the translation of a capped mRNA. An eIF4G -eIF4E complex, but not eIF4G alone, was required to restore translati on.