INHIBITION OF HOST-CELL TRANSCRIPTION BY POLIOVIRUS - CLEAVAGE OF TRANSCRIPTION FACTOR CREB BY POLIOVIRUS-ENCODED PROTEASE 3C(PRO)

Host cell RNA polymerase II-mediated transcription is inhibited by pol iovirus infection, Previous studies from our laboratory showed that ac tivated transcription from a cyclic AMP-responsive element (CRE)-conta ining promoter was severely inhibited in extracts prepared from poliov irus-infected HeLa cells compared to those from mock-infected cells. H ere we demonstrate that the CRE-binding protein, CREB, is specifically cleaved by the poliovirus encoded protease 3C(pro) both in vitro and in virus-infected cells. The proteolytic cleavage of CREB leads to a s ignificant loss of its DNA binding as well as transcriptional activity , Additionally, we demonstrate that the phosphorylated, transcriptiona lly active form of CREB is cleaved by the viral protease in vitro. The results presented here suggest that a direct cleavage of CREB by the viral protease 3C(pro) leads to inhibition of CREB-activated transcrip tion in poliovirus-infected HeLa cells.