MONENSIN AND NIGERICIN PREVENT THE INHIBITION OF HOST TRANSLATION BY POLIOVIRUS, WITHOUT AFFECTING P220 CLEAVAGE

Addition of monensin or nigericin after poliovirus entry into HeLa cel ls prevents the inhibition of host protein synthesis by poliovirus. Th e infected cells continue to synthesize cellular proteins at control l evels for at least 8 h after infection in the presence of the ionophor e, Cleavage of p220 (gamma subunit of eukaryotic initiation factor 4 [ eIF-4 gamma]), a component of the translation initiation factor eIF-4F , occurs to the same extent in poliovirus-infected cells whether or no t they are treated with monensin, Two hours after infection there is n o detectable intact p220, but the cells continue to translate cellular mRNAs for several hours at levels similar to those in uninfected cell s, Nigericin or monensin prevented the arrest of host translation at a ll the multiplicities of poliovirus infection tested, At high multipli cities of infection, an unprecedented situation was found: cells synth esized poliovirus and cellular proteins simultaneously. Superinfection of vesicular stomatitis virus-infected HeLa cells with poliovirus led to a profound inhibition of vesicular stomatitis virus protein synthe sis, while nigericin partially prevented this blockade, Drastic inhibi tion of translation also took place in influenza virus-infected Vero c ells treated with nigericin and infected with poliovirus. These findin gs suggest that the translation of newly synthesized mRNAs is dependen t on the integrity of p220, while ongoing cellular protein synthesis d oes not require an intact p220, The target of ionophore action during the poliovirus life cycle was also investigated, Addition of nigericin at any time postinfection profoundly blocked the synthesis of virus R NA, whereas viral protein synthesis was not affected if nigericin was added at 4 h postinfection, These results agree well with previous fin dings indicating that inhibitors of phospholipid synthesis or vesicula r traffic interfere with poliovirus genome replication, Therefore, the action of nigericin on the vesicular system may affect poliovirus RNA synthesis. In conclusion, monensin and nigericin are potent inhibitor s of poliovirus genome replication that prevent the shutoff of host tr anslation by poliovirus while still permitting cleavage of p220.