COMPARISON OF PICORNAVIRAL IRES-DRIVEN INTERNAL INITIATION OF TRANSLATION IN CULTURED-CELLS OF DIFFERENT ORIGINS

We recently compared the efficiency of six picornaviral internal ribos ome entry segments (IRESes) and the hepatitis C virus (HCV) IRES for t heir ability to drive internal initiation of translation invitro. Here we present the results of a similar comparison performed in six diffe rent cultured cell lines infected with a recombinant vaccinia virus ex pressing the T7 polymerase and transfected with dicistronic plasmids. The IRESes could be divided into three groups:(i) the cardiovirus and aphthovirus IRESes (and the HCV element) direct internal initiation ef ficiently in all cell lines tested; (ii) the enterovirus and rhinoviru s IRESes are at least equally efficient in several cell lines, but are extremely inefficient in certain cell types; and (iii) the hepatitis A virus IRES is incapable of directing efficient internal initiation i n any of the cell lines used (including. human hepatocytes). These are the same three groups found when IRESes were classified according to their activities in vitro, or according to sequence homologies. In a m ouse neuronal cell line, the poliovirus and other type I IRESes were n ot functional in an artificial bicistronic context. However, infectiou s poliovirions were produced efficiently after transfection of these c ells with a genomic length RNA. Furthermore, activity of the type I IR ESes was dramatically increased upon co-expression of the poliovirus 2 A proteinase, demonstrating that while IRES efficiency may vary consid erably from one cell type to another, at least in some cases viral pro teins are capable of overcoming cell-specific translational defects.